| Date |
June 29, 2011 |
| Speaker |
Prof. Keiko Udaka, Department of Immunology, Kochi Medical School |
| Title |
Development of a peptide immunotherapy for malignant tumors |
| Abstract |
Unlike its soluble counterpart, antibody, antigen recognition by T cells is restricted to
a peptide presented by a major Histocompatibility Complex (MHC) molecule. This is good to
confine T cell's attention to cell-associated antigens as well as to maximize the chance
of encountering cognate antigens within a limited space of the lymphoid organs. However,
it inevitably requires an MHC molecule to be able to present a variety of peptides to cover
diverse antigens. On the other hand, the larger the variety of peptides to be presented in
a MHC molecule the smaller the copy number of a particular peptide to be presented on an
antigen presenting cell. MHC molecules seem to have dealt with this dilemma by developing
a peptide binding cleft that can present a limited set, 1 in 100-200 random peptides to be precise.
In order to compensate for the limit of presentable peptides MHC genes appear to have accumulated
the allelic variants over a period of evolution. This strategy would be most effective if a new allele
binds different peptides from the wild type. We examined the peptide repertoire between three HLA
class I molecules and found that HLA-A alleles have evolved in a direction to gain a distinct peptide repertoire.
We also present the data from the currently running clinical trial of an allele-specific peptide immunotherapy
for malignant tumors. |
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