Antigen presenting cells.

Abstract

A great deal has been learned over the past few years regarding the molecular biology of antigen presentation. These discoveries have been possible in part because of acquisition of protein sequencing data regarding class I and class II MHC molecules and in part because of X-ray crystallographic analysis of the three-dimensional structures of these molecules. These discoveries have merged nicely with detailed immunologic studies delineating the 'minimal antigenic peptides' of complex protein antigens. All of these studies strongly confirm the belief that the antigen-specific interaction of T cells with antigen in the context of antigen presenting cells is exquisitely specific. The process of 'trimolecular complex' formation involves binding interactions between antigenic peptide, class I or class II MHC molecules and the antigen-specific T cell receptor. One of the key functions of antigen presenting cells involves the 'processing' of complex protein antigens so as to allow for the interaction of the 'minimal antigenic peptide' with the appropriate class I or class II MHC molecule. A substantial body of evidence now indicates that the interaction of processed antigenic peptides and class II MHC molecules involves a binding interaction with a significant binding affinity and a slow dissociation constant. In addition to antigen-specific binding interactions which govern antigen presentation, there are a variety of antigen-independent and MHC-independent factors which greatly augment the process of antigen presentation. Along with differences in antigen processing, these factors probably account for the qualitative and quantitative differences seen between the various cell types involved in antigen presentation. There may be a substantial amount of antigen which associates with the antigen presenting cell surface in an MHC-independent fashion associated with so-called 'non-MHC peptide binding structures'. However, if the trimolecular complex theory is to be satisfied, antigen bound to these structures ultimately must become associated with the MHC restricting element in order to effectively engage the antigen-specific T cell receptor. Antigen presenting cells differ in their sensitivity to lymphokines and inflammatory mediators which augment antigen presentation. In addition, antigen presenting cells differ in their capacity to secrete or express membrane-bound costimulatory molecules, such as interleukin 1. Finally, factors which promote the cellular adherence of antigen presenting cells with T cells greatly augment the process of antigen presentation.(ABSTRACT TRUNCATED AT 400 WORDS)