The role of idiotype-specific immunity in antigen receptor diversity

[摘要] Lymphocytes express antigen receptors which are formed by re-arrangement of gene segments. Mutations acquired during this process, predominantly in the complementarity determining regions (CDRs), result in generation of non-germline sequences.Through analysing the CDR3 sequence, this study attempts to determine whether editing of the lymphocyte repertoire is present in an HLA-dependant manner. Data presented demonstrates a decrease frequency of CDR3-derived HLA-A2 binding peptides in HLA-A2+ donors (0.03% (SYFPEITHI) and 0.35% (BIMAS)) compared with HLA-A2- donors (0.24% (SYFPEITHI, p=0.01) and 0.54% (BIMAS, p=0.19)). Trends similar to those seen in HLA-A2 were observed in other HLA alleles as well suggesting that there may be a process by which potentially dangerous B cell populations are edited from the B cell repertoire.Similar analysis of the TCR CDR3 did not reveal any such process in all of the HLA alleles tested suggesting that there is no immunoediting of the T cell repertoire. Simultaneously, this study attempts to determine the processing and presentation of CDR3-derived peptides at the cell surface using lymphocyte antigen receptor models containing CDR3-encoded viral epitopes.The apparent presence of these peptides on the cell surface leads to the hypothesis that antibodies enter the antigen processing pathway and potentially deliver an immunogenic peptide to a target cell.Using antibodies specific for B cells, this study has shown that cells labelled with an antibody-peptide complex are targeted and lysed by cytotoxic CD4+ T cells in a peptide-specific manner. The use of such technology in antibody immunotherapy may be of considerable therapeutic benefit.

[发布机构] University:University of Birmingham;Department:Institute of Cancer Studies

[关键词] Q Science;QR Microbiology;QR180 Immunology