The MBP-reactive repertoire is shaped by recognition of minor histocompatibility antigens

While it is known that the degeneracy of T-cell antigen recognition is involved in many aspects of T cell-immunology, its importance in the selection of the T cell repertoire remains an aspect to be better investigated. Here we examined if an intrathymic degenerate T cell recognition mechanism shapes the myelin basic protein (MBP)-reactive repertoire inducing resistance to experimental autoimmune encephalomyelitis (EAE) in some MHC and/or minor histocompatibility antigens (MiHAs) heterozygous F1 mice bearing the H-2(s) susceptibility allele. We found a considerable degree of cross-reactivity between MBP and MiHAs encoded in various EAE resistant mouse strains: (1) MBP-specific T cells can be re-stimulated in vitro by cells expressing these MiHAs and maintain their encephalitogenic activity, and (2) lymphoid cells from parental strains that generate EAE resistant F1 hybrids can induce disease relapse when injected into EAE-susceptible hosts. The results suggest that heterozygosity, through the degeneracy of T cell antigen recognition mechanism, may provide further means to constrain the potential autoreactive repertoire.