Diverse roles of non-diverse molecules: MHC class Ib molecules in host defense and control of autoimmunity

Abstract

While the prime function of classical MHC class I molecules (MHC-I) is to present peptide antigens to pathogen-specific cytotoxic T cells, non-classical MHC-I antigens perform a diverse array of functions in both innate and adaptive immunity. In this review we summarize recent evidence that non classical MHC-I molecules are not only recognized by pathogen-specific T cells but that they also serve as immunoregulatory molecules by stimulating a number of distinct non-conventional T cell subsets.

Figure 1. Different peptide:Qa-1^b ligands trigger varied responses by Qa-1^b-specific CD8 T cells

Left, CD8 T cells expressing TCRs specific for pathogen-derived peptide bound to Qa-1^b are stimulated to employ anti-pathogen effector activities. Middle, Dynamic interplay between TCR activation and CD94-NKG2A inhibition on a CD8 T_reg determines the fate of the autoreactive CD4 T cell. Here, TCRs of CD8 T_reg cells recognize a peptide from the TCR-Vβ of an autoreactive CD4 T cell presented by Qa-1^b. Qa-1^b also presents Qdm peptide that engages inhibitory CD94-NKG2A receptors. Right, TCR mediates CD8 T_reg recognition of a peptide derived from the signal sequence of Hsp60 presented by Qa-1^b. The CD8 T_reg is signaled to control an intermediate-affinity, potentially self-reactive CD4 T cell.