Rules for peptide binding to MHC class II molecules.

CD4+ T lymphocytes recognize peptide fragments of antigens that lie in the antigen binding pocket of class II major histocompatibility complex (MHC) molecules expressed on antigen-presenting cells. Specificity of T cells is determined by structural features of both the MHC molecule and antigenic peptide. MHC class II amino acid sequences are highly polymorphic within a population, and correlate with individual differences in response to infectious agents, vaccines, tumour antigens, and autoantigens. In the last few years several important breakthroughs and technological advances have made it possible to clarify the role of polymorphism and the molecular events in peptide interaction with major histocompatibility complex (MHC) class II proteins. The X-ray structural analysis of a MHC class II molecule together with the use of peptide libraries has permitted determination of the structural features of the complex between peptide antigen fragments and MHC class II proteins. The purpose of this article is to review our own studies and those of others on the requirements for peptide-class II molecule interaction and discuss possible implications for active immune intervention.