Antibodies that recognize red blood cell antigens
Compositions and methods of using antibodies that are able to recognize single amino acid polymorphisms in a protein are provided. Compositions are disclosed which may be used for blood typing or to block hemolytic transfusion reactions and/or hemolytic disease of the fetus and newborn.
1. An isolated antibody or fragment thereof that binds to a Kell blood group antigen KEL1 (K) and blocks a hemolytic transfusion reaction, which isolated antibody or fragment thereof comprises:
a heavy chain comprising:
CDR1 shown in SEQ ID NO: 25,
CDR2 shown in SEQ ID NO: 26, and
CDR3 shown in SEQ ID NO: 27;
and
a light chain comprising:
CDR1 shown in SEQ ID NO: 28,
CDR2 shown in SEQ ID NO: 29, and
CDR3 shown in SEQ ID NO: 30.
2. The antibody or fragment of claim 1 , wherein the antibody or fragment recognizes a single amino acid polymorphism.
3. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof is selected from the group consisting of: (a) a whole immunoglobulin molecule; (b) an scFv; (c) a Fab fragment; (d) an F(ab′) 2 ; and (e) a disulfide linked Fv.
4. The antibody or fragment thereof according to claim 1 , which comprises a heavy chain immunoglobulin constant domain selected from the group consisting of: (a) a human IgM constant domain; (b) a human IgG1 constant domain; (c) a human IgG2 constant domain; (d) a human IgG3 constant domain; (e) a human IgG4 constant domain; and (f) a human IgA1/2 constant domain.
5. The antibody or fragment thereof according to claim 1 , which comprises a light chain immunoglobulin constant domain selected from the group consisting of: (a) a human Ig kappa constant domain; and (b) a human Ig lambda constant domain.
6. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof is a mouse IgG1, IgG2a, IgG2b, IgG2c, or IgG3.
7. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof binds to an antigen with an affinity constant (K D ) of less than 1×10 −8 M.
8. The antibody or fragment thereof according to claim 1 , wherein the heavy chain comprises SEQ ID NO: 1.
9. The antibody or fragment thereof according to claim 1 , wherein the light chain comprises SEQ ID NO: 5.
10. The antibody or fragment thereof according to claim 1 , wherein the heavy chain is selected from SEQ ID NOs: 21-24.
11. The antibody or fragment thereof according to claim 6 , wherein the antibody or fragment thereof is a mouse IgG2a.
12. The antibody or fragment thereof according to claim 6 , wherein the antibody or fragment thereof is a mouse IgG3.
13. The antibody or fragment thereof according to claim 1 , wherein the heavy chain further comprises modification of Fc domain to eliminate effector function.
14. The antibody or fragment thereof according to claim 1 , wherein the heavy chain and/or light chain comprise in frame domains to suppress immune responses.
15. The antibody or fragment thereof according to claim 1 , wherein the heavy chain and/or light chain comprise chemical moieties to suppress immune responses.