Self-Peptidome Variation Shapes Individual Immune Responses. Issue 5 (May 2021) - Pontarotti, Pierre
Abstract : The relationship between human genetic variation and disease has not been fully elucidated. According to the present view on infectious diseases pathogen resistance is linked to human leukocyte antigen (HLA) class I/II variants and their individual capacity to present pathogen-derived peptides. Yet, T cell education in the thymus occurs through negative and positive selection, and both processes are controlled by a combination of HLA class I/II variants and peptides from the self. Therefore, the capacity of given HLA class I/II variants to bind pathogen-derived peptides is only one part of the selective process to generate effective immune responses. We thus propose that peptidome variation contributes to shaping T cell receptor (TCR) repertoires and hence individual immune responses, and that this variation represents inherent modulator epitopes. Highlights: TCR repertoires emerge in the thymus in each individual as T cells undergo positive and negative selection. T cell education is controlled by the combination of HLA class I/II molecules and their peptide pools (peptidome). HLA class I/II molecules are highly plastic in human populations but the peptidome is also a source of variation. Hence combined diversity of HLA class I/II molecules and of self-peptides shapes individual immune responses. Self-peptide variants that affect T cell repertoires represent inherent modulator epitopes.