Molecular relationship between private and public H-2 antigens as determined by antigen redistribution method.

Abstract

Classical H-2 antigens can be divided into two, not very sharply defined groups, private and public . Private H-2 antigens (1) have a restricted strain distribution : among inbred strains they are found in only one haplotype of independent origin ; public H-2 antigens (2), on the other hand, are shared by at least two, and quite often by a large number of unrelated haplotypes . Private H-2 antigens are believed to be controlled by alleles of two loci at the opposite ends of the H-2 complex, the H-2K locus in the K region, and the H-2D locus in the D region . In agreement with this belief, the antigens can be arranged in two series, where members of each series are mutually exclusive (3) . No such arrangement is possible for the public H-2 antigens and the nature of the genetic control of these antigens has long been a matter of controversy .According to the traditional interpretation of the H-2 complex (4), the public antigens are controlled by separate regions located between the K and D regions within the complex . According to the two-locus model (5), public H-2 antigens reside in the same molecules as the private ones and are controlled either by the H-2K or H-2D loci, or both . The two-locus model fits better the available data than the traditional multi-locus model (6) . Also, the former model is supported by the results of transplantation analysis demonstrating that only the peripheral regions of the H-2 complex are involved in rapid skin-graft rejection (7) . However, a formal proof that the serologically detectable public H-2 antigens are coded for by the K and D regions has never been provided . As a matter of fact, most recent developments (8, 9, cf. Discussion) suggest that an across the board assignment of public antigens to K and D regions could not be justified . Despite these developments, many investigators accept the two-locus model as an established fact and rely on it in their interpretation of the H-2 system . At this stage it is, therefore, critical to test whether the serologically detectable public H-2 antigens conform to the predictions of the two-locus model .We have recently developed a method that can be used to examine molecular relationships among various cell membrane antigens . The method is based on the observation that under certain circumstances, antigens coated with alloanti-* This investigation was supported by grant

Molecular Heterogeneity of H‐2 Antigens

“…Studies ofK^ and K'' products by Neauport-Sautes et al (1978), failed, as did the previous studies (Hauptfeld & Klein 1975), to disclose any mlecular heterogeneity. We have shown, however, that the K'' region products comprise at least two serologically distinct molecules .…”

Ia Antigens: Their Serology, Molecular Relationships, and their role in Allograft Reactions

“…The authors also suggested using the method for the detection and definition of la antibodies in complex sera that could not be analyzed by the use of appropriate H-2 recombinant strains (Hauptfeld et al 1975a). A systematic study of topographical relationships of H-2 (Hauptfeld & Klein 1975) and la antigens (Klein et al 1976, and unpublished data) then took place. The purpose of the latter studies was to establish, for as many Ia antigens as possible, whether these antigens are carried by the same or by different molecules or molecular complexes and thus whether they are coded for by the same or by different Ia loci.…”

“…This situation is analogous to that observed with the classical H-2 antigens coded for by the K and D regions. The authors have shown that the H-2K and H-2D molecules each carry one private and several public antigens (Hauptfeld & Klein 1975). In both the classical H-2 and the la antigens, private antigens fully characterize individual molecules, and it is important, therefore, to concentrate efEorts on deflning these antigens rather than expanding the la chart ad absurdum via public la antigens.…”

Immunochemical evidence for an additional H-2 region closely linked to H-2D.

“…The two locus H-2 model postulates that there is a single gene product for each K and D region and that the genes coding for these two molecules evolved by gene duplication (1). Limited data corroborating the existence of one K or one D region product each expressing both private and public specificities has been reported in chemical studies (2) and in surface redistribution studies (3,4), although other recent studies have shown that in one combination the D region molecules reactive with antisera detecting private and public H-2 specificities do not co-cap on the lymphocyte membrane (5). Since capping depends on accessibility of antigenic determinants to the reagents used, a variety of interpretations of these capping studies are possible.…”