Compared with the MHC of typical mammals, the chicken MHC is smaller and simpler, with only two class I genes found in the B12 haplotype. We make five points to show that there is a singledominantly expressed class I molecule that can have a strong effect on MHC function. First, we find only one cDNA for two MHC haplotypes (B14 and B15) and cDNAs corresponding to two genes for the other six (B2, B4, B6, B12, B19, and B21). Second, we find, for the B4, B12, and B15 haplotypes, that one cDNA is at least 10-fold more abundant than the other. Third, we use 2D gel electrophoresis of class I molecules from pulse-labeled cells to show that there is only one heavy chain spot for the B4 and B15 haplotypes, and one major spot for the B12 haplotype. Fourth, we determine the peptide motifs for B4, B12, and B15 cells in detail, including pool sequences and individual peptides, and show that the motifs are consistent with the peptides binding to models of the class I molecule encoded by the abundant cDNA. Finally, having shown for three haplotypes that there is a single dominantly expressed class I molecule at the level of RNA, protein, and antigenic peptide, we show that the motifs can explain the striking MHC-determined resistance and susceptibility to Rous sarcoma virus. These results are consistent with the concept of a ''minimal essential MHC'' for chickens, in strong contrast to typical mammals.antigen presentation ͉ avian ͉ essential ͉ evolution ͉ minimal

The high polymorphism of classical Mhc molecules found in mammals is not simply the result of strong selection for pathogen resistance in the recent past, since there are virtually no examples of diseases caused by infectious pathogens for which resistance is determined by particular Mhc haplotypes, and in the best-studied case, a particular aspect of malaria in humans, the selection is remarkably weak. We discuss three possibilities to explain high polymorphism in mammals: accumulating, merging and boosting. The mammalian Mhc is complicated and redundant, so that every Mhc haplotype may give some level of resistance due to multiple classical Mhc genes as well as other disease resistance genes; this frustrates the attempts to demonstrate selection for disease resistance. We have looked at two vertebrate groups that may represent two extreme examples of selection for Mhc polymorphism. Birds, like mammals, have highly a polymorphic Mhc that determines strong allograft rejection. However, chickens have a much smaller, compact and simpler Mhc than mammals, as though the Mhc has been stripped down to the essentials during evolution. The selection on a single Mhc gene should be much stronger than on a large multigene family and, in fact, there are a number of viral diseases for which resistance and susceptibility are determined by particular chicken Mhc haplotypes. We have determined the peptide motifs for the chicken class I molecules from a number of haplotypes, which may explain some disease associations quite simply. On the other hand, salamanders have very low Mhc polymorphism and slow allograft rejection. We have isolated axolotl Mhc molecules and shown that they cosegregate with the locus that determines graft rejection in the axolotl, have only a few alleles and only weakly stimulate axolotl T lymphocytes in mixed lymphocyte culture. We believe that salamanders have classical Mhc molecules but most T cells do not recognize them, so that there is no strong selection for polymorphism.

Little is known about the structure of major histocompatibility complex (MHC) molecules outside of mammals. Only one class I molecule in the chicken MHC is highly expressed, leading to strong genetic associations with infectious pathogens. Here, we report two structures of the MHC class I molecule BF2*2101 from the B21 haplotype, which is known to confer resistance to Marek's disease caused by an oncogenic herpesvirus. The binding groove has an unusually large central cavity, which confers substantial conformational flexibility to the crucial residue Arg9, allowing remodeling of key peptide-binding sites. The coupled variation of anchor residues from the peptide, utilizing a charge-transfer system unprecedented in MHC molecules, allows peptides with conspicuously different sequences to be bound. This promiscuous binding extends our understanding of ways in which MHC class I molecules can present peptides to the immune system and might explain the resistance of the B21 haplotype to Marek's disease.

The TCR has been identified in several species as a heterodimer of two variable chains (reviewed in reference 1) that is associated with a set of invariant polypeptides collectively referred to as CD3 . MHC-restricted antigen recognition by both cytotoxic (mostly CD8') and helper (mostly CD4') T cells is mediated by clonotypic heterodimers of the a/ß type, while a second type of CD3-associated TCR, termed y/S, has recently been discovered on a small subpopulation of human (2) and mouse (3) T cells . mAbs to the TCR and CD3 molecules have been instrumental to the discovery and analysis of the TCR complex . Recent work in the mouse system has especially profited from the generation of mAbs to Vß segments expressed at a frequency detectable in unimmunized T cell populations (4-7), and to the invariant CD3E chain (8) . No mAb to . a constant determinant of the mouse TCR-a/ß is available, however, that could be used to discriminate TCR-a/ß and TCR-,y/8 expressing T cells and thymocytes. In the rat system, analysis of T cell maturation and activation has been hampered by a complete lack of TCR-and CD3-specific monoclonal reagents, despite an otherwise excellent collection of mAbs to cell surface molecules .Here, we describe a new mAb, termed R73, that detects a rat pan T cell surface antigen with the predicted properties of the TCR-a/ß on mature and immature cells of the T cell lineage and reports its functional effects on resting T lymphocytes . Materials and MethodsAnimals. Young adult Wistar and Lewis rats ofboth sexes were obtained from the animal quarters of the Max Planck Institute for Biochemistry, Martinsried, FRG, or from the Zentralinstitut für Versuchstierzucht, Medizinische Hochschule Hannover, FRG. Results obtained did not vary significantly between both strains .Immunization and Cell Fusion . Spleen cells from a BALB/c mouse alternately immunized intraperitoneally with rat T blasts and rat erythrocytes (it was also intended to generate an mAb to rat LFA-3) were fused 3 d after an intravenous injection of 10' rat erythrocytes with This work was funded by a grant from the Bundesministerium für Forschung und Technologie . Generation of the R73 cell line was funded by Genzentrum e.V. J . Exp. MED.

Minor histocompatibility (H) antigens can be peptides derived from cellular proteins that are presented on the cell surface by major histocompatibility complex (MHC) class I molecules. This is similar to viral antigens, because in both cases cytotoxic T lymphocytes (CTLs) recognize artificially produced peptides loaded on target cells. Naturally processed minor H peptides were found to be similar to those artificial CTL-epitopes, as far as size and hydrophobicity is concerned. The peptides studied were isolated from a transfectant that expressed a model CTL-defined antigen, beta-galactosidase, from male cells that express H-Y, which has been known operationally since 1955, and from cells that express H-4, known since 1961.