Human monoclonal antibody

1. An isolated anti-human CD81 antibody that binds to a peptide region consisting of the amino acid sequence of residues 80 to 175 in the amino acid sequence of SEQ ID NO: 22, wherein the binding affinity of the antibody to at least one human CD81 variant selected from the group consisting of the following (1) to (13) is less than 40% of that to the human CD81 polypeptide comprising the amino acid sequence of SEQ ID NO:22;

(1) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that tyrosine at residue 127 is substituted with phenylalanine or tryptophan;

(2) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that alanine at residue 130 is substituted with threonine or valine;

(3) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that valine at residue 135 is substituted with alanine or leucine;

(4) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that aspartic acid at residue 137 is substituted with alanine or glutamic acid;

(5) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that alanine at residue 143 is substituted with threonine or valine;

(6) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that histidine at residue 151 is substituted with alanine or arginine;

(7) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that leucine at residue 154 is substituted with alanine or isoleucine;

(8) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that glycine at residue 158 is substituted with alanine or serine;

(9) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that alanine at residue 164 is substituted with threonine or valine;

(10) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that serine at residue 168 is substituted with alanine or threonine;

(11) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that valine at residue 169 is substituted with alanine or leucine;

(12) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that leucine at residue 170 is substituted with alanine or isoleucine; and

(13) CD81 variant comprising the amino acid sequence of SEQ ID NO:22 except that asparagine at residue 172 is substituted with alanine or glutamine.

2. The antibody of claim 1 , wherein the binding affinity of the antibody to each of the above-identified human CD81 variants (9) and (11) is less than 40% of that to the human CD81 polypeptide comprising the amino acid sequence of SEQ ID NO:22.

3. An isolated antibody that binds to the human CD81 polypeptide comprising the amino acid sequence of SEQ ID NO:22, wherein binding of the antibody to the human CD81 polypeptide is competitively inhibited by the antibody of claim 1 .

4. An isolated antibody that binds to the human CD81 polypeptide comprising the amino acid sequence of SEQ ID NO:22, wherein binding of the antibody to the human CD81 polypeptide is competitively inhibited by the antibody of claim 1 , and wherein the antibody has a suppressive effect on T cell migration.

5. An isolated anti-human CD81 antibody, which comprises all 6 complementary determining regions (CDRs) described in any one of the following groups 1 to 24:

Group 1

(a-1) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-1) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-1) a CDR comprising the amino acid sequence of SEQ ID NO:3,

(d-1) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-1) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-1) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 2

(a-2) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-2) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-2) a CDR comprising the amino acid sequence of SEQ ID NO:37,

(d-2) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-2) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-2) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 3

(a-3) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-3) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-3) a CDR comprising the amino acid sequence of SEQ ID NO:40,

(d-3) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-3) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-3) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 4

(a-4) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-4) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-4) a CDR comprising the amino acid sequence of SEQ ID NO:43,

(d-4) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-4) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-4) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 5

(a-5) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-5) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-5) a CDR comprising the amino acid sequence of SEQ ID NO:46,

(d-5) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-5) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(t-5) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 6

(a-6) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-6) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-6) a CDR comprising the amino acid sequence of SEQ ID NO:49,

(d-6) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-6) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-6) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 7

(a-7) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-7) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-7) a CDR comprising the amino acid sequence of SEQ ID NO:52,

(d-7) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-7) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-7) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 8

(a-8) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-8) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-8) a CDR comprising the amino acid sequence of SEQ ID NO:43,

(d-8) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-8) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-8) a CDR comprising the amino acid sequence of SEQ ID NO:55

Group 9

(a-9) a CDR comprising the amino acid sequence of SEQ ID NO:60,

(b-9) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-9) a CDR comprising the amino acid sequence of SEQ ID NO:3,

(d-9) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-9) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-9) a CDR comprising the amino acid sequence of SEQ ID NO:61

Group 10

(a-10) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-10) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-10) a CDR comprising the amino acid sequence of SEQ ID NO:66,

(d-10) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-10) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-10) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 11

(a-11) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-11) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-11) a CDR comprising the amino acid sequence of SEQ ID NO:3,

(d-11) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-11) a CDR comprising the amino acid sequence of SEQ ID NO:69, and

(f-11) a CDR comprising the amino acid sequence of SEQ ID NO:70

Group 12

(a-12) a CDR comprising the amino acid sequence of SEQ ID NO:60,

(b-12) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-12) a CDR comprising the amino acid sequence of SEQ ID NO:66,

(d-12) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-12) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-12) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 13

(a-13) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-13) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-13) a CDR comprising the amino acid sequence of SEQ ID NO:3,

(d-13) a CDR comprising the amino acid sequence of SEQ ID NO:77,

(e-13) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-13) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 14

(a-14) a CDR comprising the amino acid sequence of SEQ ID NO:80,

(b-14) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-14) a CDR comprising the amino acid sequence of SEQ ID NO:3,

(d-14) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-14) a CDR comprising the amino acid sequence of SEQ ID NO:81, and

(f-14) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 15

(a-15) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-15) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-15) a CDR comprising the amino acid sequence of SEQ ID NO:66,

(d-15) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-15) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-15) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 16

(a-16) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-16) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-16) a CDR comprising the amino acid sequence of SEQ ID NO:90,

(d-16) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-16) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-16) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 17

(a-17) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-17) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-17) a CDR comprising the amino acid sequence of SEQ ID NO:52,

(d-17) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-17) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-17) a CDR comprising the amino acid sequence of SEQ ID NO:93

Group 18

(a-18) a CDR comprising the amino acid sequence of SEQ ID NO:98,

(b-18) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-18) a CDR comprising the amino acid sequence of SEQ ID NO:3,

(d-18) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-18) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-18) a CDR comprising the amino acid sequence of SEQ ID NO:99

Group 19

(a-19) a CDR comprising the amino acid sequence of SEQ ID NO:60,

(b-19) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-19) a CDR comprising the amino acid sequence of SEQ ID NO:3,

(d-19) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-19) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-19) a CDR comprising the amino acid sequence of SEQ ID NO:99

Group 20

(a-20) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-20) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-20) a CDR comprising the amino acid sequence of SEQ ID NO:90,

(d-20) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-20) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-20) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 21

(a-21) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-21) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-21) a CDR comprising the amino acid sequence of SEQ ID NO:3,

(d-21) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-21) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-21) a CDR comprising the amino acid sequence of SEQ ID NO:55

Group 22

(a-22) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-22) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-22) a CDR comprising the amino acid sequence of SEQ ID NO:66,

(d-22) a CDR comprising the amino acid sequence of SEQ ID NO:110,

(e-22) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-22) a CDR comprising the amino acid sequence of SEQ ID NO:6

Group 23

(a-23) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-23) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-23) a CDR comprising the amino acid sequence of SEQ ID NO:3,

(d-23) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-23) a CDR comprising the amino acid sequence of SEQ ID NO:5, and

(f-23) a CDR comprising the amino acid sequence of SEQ ID NO:115

Group 24

(a-24) a CDR comprising the amino acid sequence of SEQ ID NO:1,

(b-24) a CDR comprising the amino acid sequence of SEQ ID NO:2,

(c-24) a CDR comprising the amino acid sequence of SEQ ID NO:90,

(d-24) a CDR comprising the amino acid sequence of SEQ ID NO:4,

(e-24) a CDR comprising the amino acid sequence of SEQ ID NO:120, and

(f-24) a CDR comprising the amino acid sequence of SEQ ID NO:6.

6. The antibody of claim 5 , which comprises the combination of the light chain variable region and the heavy chain variable region described in any one of the following groups 25 to 48:

Group 25

(g-1) a light chain variable region comprising the above-identified CDRs (a-1) to (c-1); and

(h-1) a heavy chain variable region comprising the above-identified CDRs (d-1) to (f-1),

Group 26

(g-2) a light chain variable region comprising the above-identified CDRs (a-2) to (c-2); and

(h-2) a heavy chain variable region comprising the above-identified CDRs (d-2) to (f-2),

Group 27

(g-3) a light chain variable region comprising the above-identified CDRs (a-3) to (c-3); and

(h-3) a heavy chain variable region comprising the above-identified CDRs (d-3) to (f-3),

Group 28

(g-4) a light chain variable region comprising the above-identified CDRs (a-4) to (c-4); and

(h-4) a heavy chain variable region comprising the above-identified CDRs (d-4) to (f-4),

Group 29

(g-5) a light chain variable region comprising the above-identified CDRs (a-5) to (c-5); and

(h-5) a heavy chain variable region comprising the above-identified CDRs (d-5) to (f-5),

Group 30

(g-6) a light chain variable region comprising the above-identified CDRs (a-6) to (c-6); and

(h-6) a heavy chain variable region comprising the above-identified CDRs (d-6) to (f-6),

Group 31

(g-7) a light chain variable region comprising the above-identified CDRs (a-7) to (c-7); and

(h-7) a heavy chain variable region comprising the above-identified CDRs (d-7) to (f-7),

Group 32

(g-8) a light chain variable region comprising the above-identified CDRs (a-8) to (c-8); and

(h-8) a heavy chain variable region comprising the above-identified CDRs (d-8) to (f-8),

Group 33

(g-9) a light chain variable region comprising the above-identified CDRs (a-9) to (c-9); and

(h-9) a heavy chain variable region comprising the above-identified CDRs (d-9) to (f-9),

Group 34

(g-10) a light chain variable region comprising the above-identified CDRs (a-10) to (c-10); and

(h-10) a heavy chain variable region comprising the above-identified CDRs (d-10) to (f-10),

Group 35

(g-11) a light chain variable region comprising the above-identified CDRs (a-11) to (c-11); and

(h-11) a heavy chain variable region comprising the above-identified CDRs (d-11) to (f-11),

Group 36

(g-12) a light chain variable region comprising the above-identified CDRs (a-12) to (c-12); and

(h-12) a heavy chain variable region comprising the above-identified CDRs (d-12) to (f-12),

Group 37

(g-13) a light chain variable region comprising the above-identified CDRs (a-13) to (c-13); and

(h-13) a heavy chain variable region comprising the above-identified CDRs (d-13) to (f-13),

Group 38

(g-14) a light chain variable region comprising the above-identified CDRs (a-14) to (c-14); and

(h-14) a heavy chain variable region comprising the above-identified CDRs (d-14) to (f-14),

Group 39

(g-15) a light chain variable region comprising the above-identified CDRs (a-15) to (c-15); and

(h-15) a heavy chain variable region comprising the above-identified CDRs (d-15) to (f-15),

Group 40

(g-16) a light chain variable region comprising the above-identified CDRs (a-16) to (c-16); and

(h-16) a heavy chain variable region comprising the above-identified CDRs (d-16) to (f-16),

Group 41

(g-17) a light chain variable region comprising the above-identified CDRs (a-17) to (c-17); and

(h-17) a heavy chain variable region comprising the above-identified CDRs (d-17) to (f-17),

Group 42

(g-18) a light chain variable region comprising the above-identified CDRs (a-18) to (c-18); and

(h-18) a heavy chain variable region comprising the above-identified CDRs (d-18) to (f-18),

Group 43

(g-19) a light chain variable region comprising the above-identified CDRs (a-19) to (c-19); and

(h-19) a heavy chain variable region comprising the above-identified CDRs (d-19) to (f-19),

Group 44

(g-20) a light chain variable region comprising the above-identified CDRs (a-20) to (c-20); and

(h-20) a heavy chain variable region comprising the above-identified CDRs (d-20) to (f-20),

Group 45

(g-21) a light chain variable region comprising the above-identified CDRs (a-21) to (c-21); and

(h-21) a heavy chain variable region comprising the above-identified CDRs (d-21) to (f-21),

Group 46

(g-22) a light chain variable region comprising the above-identified CDRs (a-22) to (c-22); and

(h-22) a heavy chain variable region comprising the above-identified CDRs (d-22) to (f-22),

Group 47

(g-23) a light chain variable region comprising the above-identified CDRs (a-23) to (c-23); and

(h-23) a heavy chain variable region comprising the above-identified CDRs (d-23) to (f-23),

Group 48

(g-24) a light chain variable region comprising the above-identified CDRs (a-24) to (c-24); and

(h-24) a heavy chain variable region comprising the above-identified CDRs (d-24) to (f-24).

7. The antibody of claim 6 , which comprises the combination of the light chain variable region and the heavy chain variable region described in any one of the following groups 49 to 72:

Group 49

(i-1) a light chain variable region comprising the amino acid sequence of SEQ ID NO:8; and

(j-1) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:10,

Group 50

(i-2) a light chain variable region comprising the amino acid sequence of SEQ ID NO:38; and

(j-2) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:10,

Group 51

(i-3) a light chain variable region comprising the amino acid sequence of SEQ ID NO:41; and

(j-3) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:10,

Group 52

(i-4) a light chain variable region comprising the amino acid sequence of SEQ ID NO:44; and

(j-4) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:10,

Group 53

(i-5) a light chain variable region comprising the amino acid sequence of SEQ ID NO:47; and

(j-5) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:10,

Group 54

(i-6) a light chain variable region comprising amino acid sequence of SEQ ID NO:50; and

(j-6) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:10,

Group 55

(i-7) a light chain variable region comprising amino acid sequence of SEQ ID NO:53; and

(j-7) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:10,

Group 56

(i-8) a light chain variable region comprising amino acid sequence of SEQ ID NO:56; and

(j-8) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:57,

Group 57

(i-9) a light chain variable region comprising amino acid sequence of SEQ ID NO:62; and

(j-9) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:63,

Group 58

(i-10) a light chain variable region comprising amino acid sequence of SEQ ID NO:67; and

(j-10) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:10,

Group 59

(i-11) a light chain variable region comprising amino acid sequence of SEQ ID NO:71; and

(j-11) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:72,

Group 60

(i-12) a light chain variable region comprising amino acid sequence of SEQ ID NO:75; and

(j-12) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:10,

Group 61

(i-13) a light chain variable region comprising amino acid sequence of SEQ ID NO:8; and

(j-13) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:78,

Group 62

(i-14) a light chain variable region comprising amino acid sequence of SEQ ID NO:82; and

(j-14) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:83,

Group 63

(i-15) a light chain variable region comprising amino acid sequence of SEQ ID NO:86; and

(j-15) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:87,

Group 64

(i-16) a light chain variable region comprising amino acid sequence of SEQ ID NO:91; and

(j-16) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:10,

Group 65

(i-17) a light chain variable region comprising amino acid sequence of SEQ ID NO:94; and

(j-17) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:95,

Group 66

(i-18) a light chain variable region comprising amino acid sequence of SEQ ID NO:100; and

(j-18) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:101,

Group 67

(i-19) a light chain variable region comprising amino acid sequence of SEQ ID NO:104; and

(j-19) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:101,

Group 68

(i-20) a light chain variable region comprising amino acid sequence of SEQ ID NO:106; and

(j-20) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:10,

Group 69

(i-21) a light chain variable region comprising amino acid sequence of SEQ ID NO:108; and

(j-21) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:57,

Group 70

(i-22) a light chain variable region comprising amino acid sequence of SEQ ID NO:111; and

(j-22) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:112,

Group 71

(i-23) a light chain variable region comprising amino acid sequence of SEQ ID NO:116; and

(j-23) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:117,

Group 72

(i-24) a light chain variable region comprising amino acid sequence of SEQ ID NO:121; and

(j-24) a heavy chain variable region comprising amino acid sequence of SEQ ID NO:122.

8. The antibody of claim 6 , which comprises the combination of the light chain and the heavy chain described in any one of the following groups 73 to 96:

Group 73

(k-1) a light chain comprising the amino acid sequence of SEQ ID NO:26; and

(l-1) a heavy chain comprising the amino acid sequence of SEQ ID NO:28,

Group 74

(k-2) a light chain comprising the amino acid sequence of SEQ ID NO:39; and

(l-2) a heavy chain comprising the amino acid sequence of SEQ ID NO:28,

Group 75

(k-3) a light chain comprising the amino acid sequence of SEQ ID NO:42; and

(l-3) a heavy chain comprising the amino acid sequence of SEQ ID NO:28,

Group 76

(k-4) a light chain comprising the amino acid sequence of SEQ ID NO:45; and

(l-4) a heavy chain comprising the amino acid sequence of SEQ ID NO:28,

Group 77

(k-5) a light chain comprising the amino acid sequence of SEQ ID NO:48; and

(l-5) a heavy chain comprising the amino acid sequence of SEQ ID NO:28,

Group 78

(k-6) a light chain comprising the amino acid sequence of SEQ ID NO:51; and

(l-6) a heavy chain comprising the amino acid sequence of SEQ ID NO:28,

Group 79

(k-7) a light chain comprising the amino acid sequence of SEQ ID NO:54; and

(l-7) a heavy chain comprising the amino acid sequence of SEQ ID NO:28,

Group 80

(k-8) a light chain comprising the amino acid sequence of SEQ ID NO:58; and

(l-8) a heavy chain comprising the amino acid sequence of SEQ ID NO:59,

Group 81

(k-9) a light chain comprising the amino acid sequence of SEQ ID NO:64; and

(l-9) a heavy chain comprising the amino acid sequence of SEQ ID NO:65,

Group 82

(k-10) a light chain comprising the amino acid sequence of SEQ ID NO:68; and

(l-10) a heavy chain comprising the amino acid sequence of SEQ ID NO: 28,

Group 83

(k-11) a light chain comprising the amino acid sequence of SEQ ID NO:73; and

(l-11) a heavy chain comprising the amino acid sequence of SEQ ID NO: 74,

Group 84

(k-12) a light chain comprising the amino acid sequence of SEQ ID NO:76; and

(l-12) a heavy chain comprising the amino acid sequence of SEQ ID NO: 28,

Group 85

(k-13) a light chain comprising the amino acid sequence of SEQ ID NO:26; and

(l-13) a heavy chain comprising the amino acid sequence of SEQ ID NO: 79,

Group 86

(k-14) a light chain comprising the amino acid sequence of SEQ ID NO:84; and

(l-14) a heavy chain comprising the amino acid sequence of SEQ ID NO: 85,

Group 87

(k-15) a light chain comprising the amino acid sequence of SEQ ID NO:88; and

(l-15) a heavy chain comprising the amino acid sequence of SEQ ID NO: 89,

Group 88

(k-16) a light chain comprising the amino acid sequence of SEQ ID NO:92; and

(l-16) a heavy chain comprising the amino acid sequence of SEQ ID NO: 28,

Group 89

(k-17) a light chain comprising the amino acid sequence of SEQ ID NO:96; and

(l-17) a heavy chain comprising the amino acid sequence of SEQ ID NO: 97,

Group 90

(k-18) a light chain comprising the amino acid sequence of SEQ ID NO: 102; and

(l-18) a heavy chain comprising the amino acid sequence of SEQ ID NO: 103,

Group 91

(k-19) a light chain comprising the amino acid sequence of SEQ ID NO: 105; and

(l-19) a heavy chain comprising the amino acid sequence of SEQ ID NO: 103,

Group 92

(k-20) a light chain comprising the amino acid sequence of SEQ ID NO: 107; and

(l-20) a heavy chain comprising the amino acid sequence of SEQ ID NO: 28,

Group 93

(k-21) a light chain comprising the amino acid sequence of SEQ ID NO: 109; and

(l-21) a heavy chain comprising the amino acid sequence of SEQ ID NO: 59,

Group 94

(k-22) a light chain comprising the amino acid sequence of SEQ ID NO: 113; and

(l-22) a heavy chain comprising the amino acid sequence of SEQ ID NO: 114,

Group 95

(k-23) a light chain comprising the amino acid sequence of SEQ ID NO: 118; and

(l-23) a heavy chain comprising the amino acid sequence of SEQ ID NO: 119,

Group 96

(k-24) a light chain comprising the amino acid sequence of SEQ ID NO: 123; and

(l-24) a heavy chain comprising the amino acid sequence of SEQ ID NO: 124.

9. An isolated antibody binding to the human CD81 polypeptide comprising the amino acid sequence of SEQ ID NO:22, wherein biding of the antibody to the human CD81 polypeptide is competitively inhibited by the antibody of claim 5 .

10. The antibody of claim 9 , which has a suppressive effect on T cell migration.

11. An isolated anti-human CD81 antibody comprising:

(a-25) a complementarity determining region (CDR) comprising the amino acid sequence SEQ ID NO:11;

(b-25) a CDR comprising the amino acid sequence of SEQ ID NO:12;

(c-25) a CDR comprising the amino acid sequence of SEQ ID NO:13;

(d-25) a CDR comprising the amino acid sequence of SEQ ID NO:14;

(e-25) a CDR comprising the amino acid sequence of SEQ ID NO:15; and

(f-25) a CDR comprising the amino acid sequence of SEQ ID NO:16.

12. The antibody of claim 11 , which comprises:

(g-25) a light chain variable region comprising the above-identified CDRs (a-25) to (c-25); and

(h-25) a heavy chain variable region comprising the above-identified CDRs (d-25) to (f-25).

13. The antibody of claim 12 , which comprises:

(i-25) a light chain variable region comprising the amino acid sequence of SEQ ID NO:18; and

(j-25) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:20.

14. The antibody of claim 12 , which comprises:

(k-25) a light chain comprising the amino acid sequence of SEQ ID NO:30; and

(l-25) a heavy chain comprising the amino acid sequence of SEQ ID NO:32.

15. An isolated antibody binding to the human CD81 polypeptide comprising the amino acid sequence of SEQ ID NO:22, wherein biding of the antibody to the human CD81 polypeptide is competitively inhibited by the antibody of claim 11 .

16. The antibody of claim 15 , which has a suppressive effect on T cell migration.

17. The antibody of claim 1 which is a humanized or human antibody.

18. A pharmaceutical composition comprising the antibody of claim 1 .