The Ia antigens.

Abstract

The Ia antigens constitute a polymorphic series of cell surface determinants. At present, their definition is mainly a genetic one, and thus any cell surface antigen which can be demonstrated to be encoded by a gene in the Ir region of the H-2 complex may be classified as an Ia antigen. There are presently three subregions of the I region defined on the basis of available recombinant haplotypes, and designated at I-A, I-B, AND I-C. Mapping of individual Ia specificities indicates that numerous specificities are determined by genes in the I-A subregion, several in the I-C subregion, and few, if any, in the I-B subregion. This may be a reflection of the state of the art, however, rather than an accurate assessment of the extent of polymorphism. The Ia antigens appear to be expressed preferentially on the B-cell subpopulation of lymphoid cells. However, with the use of sensitive techniques they have also been demonstrated on some T cells, on macrophages, on sperm cells, and on epidermal cells. The Ia antigens have also been demonstrated on several T-cell factors which appear to be involved in the immune response. Whether or not all of the Ia antigens thus localized are identical or represent overlapping specificities within the same sera remains in many cases to be determined. There are presently three ways of defining Ia specificities serologically: (1) by direct immunization between strains differing only in the I region; (2) by detection of shared Ia determinants using polyspecific sera which contain H-2K region and H-2D region antibodies but which are nevertheless specific only for Ia antigens when tested on target cells of other strains; and (3) by selective absorption of H-2K region and H-2D region antibodies from an H-2 antiserum by cells bearing these antigens but lacking (or relatively lacking Ia antigens. All three of these methods produce anti-Ia reagents of reasonable titer for use in both serological and functional experimentation. The definition of the specificity as an Ia specificity in each case requires the availability of appropriate recombinant strains to map the specificity to the Iregion. In addition, there are several correlative criteria which have been developed in order to detect Ia activity in alloantisera in the absence of the availability of appropriate recombinants for mapping of the specificity. These include the tissue distribution of the Ia antigens (namely, their predominant expression on the B-cell subpopulation), their characteristics molecular size, their association on the B-cell surface with the Fc receptor, and their lack of association with other products of the major histocompatibility complex as distinguished either chemically or by cocapping studies. These correlative criteria make it possible to distinguish probable anti-Ia reactivity in a variety of serological reactions, but the results must still be interpreted with caution until appropriate recombinants have been obtained which can map the specificities to the I region...