Self-Peptidome Variation Shapes Individual Immune Responses

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.