Method For Increasing Cd8+ Cytotoxic T Cell Responses And For Treating Multiple Sclerosis
The present invention relates generally to the field of immunology and development of autologous vaccines. More specifically, the present invention is concerned with a method of treating autoimmune disease Multiple Sclerosis (MS) by means of immunizing patients with autologous CD8 + cells activated with fragments of Myelin Basic Protein (MBP). The present invention identifies four immunogenic MBP fragments with high binding affinity to HLA-A2 and HLA-A24 receptors and discloses how to use these fragments in preparing anti-MS vaccine.
1 . A method of making an autologous T cell vaccine for the treatment of multiple sclerosis comprising:
(a) providing a population of peripheral blood mononuclear cells comprising T cells from a patient to be treated with the vaccine;
(b) reducing the population of CD4 + T cells;
(c) adding a MS associated antigen and optionally antigen presenting cells; and
(d) repeating step (c) one or more times.
2 . The method of claim 1 wherein said MS associated antigen is selected from the group consisting of myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein and combinations thereof.
3 . The method of claim 1 wherein said MS associated antigen comprises a sequence set forth in any one of SEQ ID NOS:1-4.
4 . The method of claim 1 wherein said MS associated antigen comprises amino acids 83-99 or 151-170 of MBP.
5 . The method of claim 1 wherein step (c) further comprises adding IL-2.
6 . The method of claim 1 wherein step (c) further comprises adding a mitogen.
7 . The method of claim 6 wherein said mitogen is selected from the group consisting of phytohemagglutinin, conconavalin A, pokeweed mitogen, and monoclonal antibodies to CD3.
8 . An autologous T cell vaccine made by the method according to any one of claims 1 - 7 .
9 . A method of treating multiple sclerosis comprising administering to a patient in need thereof an autologous T cell vaccine according to claim 8 .
10 . An autologous T cell vaccine comprising an enriched population of CD8 + T cells reactive to a MS associated antigen.
11 . The vaccine of claim 10 wherein the population of CD4 + T cells is reduced.
12 . The vaccine of claim 10 wherein said MS related antigen is selected from the group consisting of myelin basic protein, proteolipid protein and myelin oligodendrocyte glycoprotein.
13 . The vaccine of claim 10 wherein said MS related antigen comprises a sequence set forth in any one of SEQ ID NOS:1-4.
14 . The vaccine of claim 10 wherein said MS related antigen comprises amino acids 83-99 or 151-170 of MBP.