Major histocompatibility complex haplotypes and the cell physiology of peptide hormones

Abstract

Speculations about the function of the major histocompatibility complex (MHC) have ranged widely over the years. Though the immune functions of the MHC have always been foremost in such speculations, there has always been a background of ideas and experiments about other functions of the complex [ 1]. While some associations of MHC and function are due to products of genes linked to the traditional MHC genes, most of the data on MHC/functional associations cannot be attributed to unknown genes, and, rather, must be explained in terms of unknown functions of known MHC gene products. The speculative basis for these unknown functions rests with a view that the products of the MHC complex evolved from primitive general systems for at the cell surface. This position was taken by Bodmer [2], Ohno [3], and Edelman [4] and, discussing the interactions of colonial tunicates, by Burnett [5] and by Scolfield and co-workers [6], by Dausset and Contu [7], and by Snell [8]. Their speculations on MHC origin appear to be better founded in truth today than they did at their first publication, because the sequence homologies between MHC antigens and a number of other proteins comprising the immunoglobulin superfamily suggest a common origin of the genes for all of these proteins, from an ancestral gene specifying a small membrane protein [9]. General properties then may be postulated as basic properties of MHC antigens. How readily can we detect such properties? A general approach to testing MHC dependence of cell phenomena has been through systems in which some aspects of can be quantitated. In such experiments, from our laboratory as well as from others, the assumption is made that while MHC antigens may modify or modulate recognition, they cannot act to abolish a specific system or to create a new, qualitatively distinct system. Thus all of the work in the area of nonimmune recognition has been on the quantitation of specific events such as cell-to-cell adhesion or the binding of hormones to specific receptors and subsequent cellular responses. Another good example of such work, on drug binding to cell surfaces, is presented by van Rood and co-workers in this volume [10]. Experiments on cell adhesion involve complicated multistage systems, but may be quantitated in vitro by measuring either the rate of single cell adhesion to