Conformational isomers of a peptide–class II major histocompatibility complex

Authors: Lovitch, Scott B.; Unanue, Emil R.

Source: Immunological Reviews, Volume 207, Number 1, October 2005 , pp. 293-313(21)

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Abstract:

Summary:

The relative plasticity of peptide binding to class II major histocompatibility complex (MHC) molecules permits formation of multiple conformational isomers by the same peptide and MHC molecule; such conformers are specifically recognized by distinct subsets of T cells. Here, we review current knowledge and recent advances in our understanding of peptide–class II MHC conformational isomerism and the mechanisms that generate distinct MHC–peptide conformers. We focus on our studies of two T-cell subsets, type A and B, which recognize distinct conformers of the dominant epitope of hen egg white lysozyme presented by I-A^k. These conformers form via different pathways and in distinct intracellular vesicles: the type A conformer forms in late endosomes upon processing of native protein, while the more flexible type B conformer forms in early endosomes and at the cell surface. In this process, H2-DM acts as a conformational editor, eliminating the type B conformer in late endosomes. Type B T cells constitute a significant component of the naïve T-cell repertoire; furthermore, self-reactive type B T cells escape negative selection and are present in abundance in the periphery. Ongoing studies should elucidate the role of type B T cells in immunity to pathogens and in autoimmune pathology.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.0105-2896.2005.00298.x

Affiliations: 1: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA

Publication date: 2005-10-01