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.

CD1 molecules play an important role in the immune system, presenting lipid-containing antigens to T and NKT cells. CD1 genes have long been thought to be as ancient as MHC class I and II genes, based on various arguments, but thus far they have been described only in mammals. Here we describe two CD1 genes in chickens, demonstrating that the CD1 system was present in the last common ancestor of mammals and birds at least 300 million years ago. In phylogenetic analysis, these sequences cluster with CD1 sequences from other species but are not obviously like any particular CD1 isotype. Sequence analysis suggests that the expressed proteins bind hydrophobic molecules and are recycled through intracellular vesicles. RNA expression is strong in lymphoid tissues but weaker to undetectable in some nonlymphoid tissues. Flow cytometry confirms expression from one gene on B cells. Based on Southern blotting and cloning, only two such CD1 genes are detected, located Ϸ800 nucleotides apart and in the same transcriptional orientation. The sequence of one gene is nearly identical in six chicken lines. By mapping with a backcross family, this gene could not be separated from the chicken MHC on chromosome 16. Mining the draft chicken genome sequence shows that chicken has only these two CD1 genes located Ϸ50 kb from the classical class I genes. The unexpected location of these genes in the chicken MHC suggests the CD1 system was present in the primordial MHC and is thus Ϸ600 million years old.evolution ͉ paralogy ͉ antigen presentation ͉ nonclassical ͉ avian M HC class I and II molecules play crucial roles in the immune system by presenting peptide antigen to T lymphocytes, as well as natural killer cells recognizing class I molecules. Both MHC class I and II genes have been described in all jawed vertebrates (including bony and cartilaginous fish) and are thought to have arisen at the same time as recombination activating, T cell receptor, and antibody genes Ϸ600 million years ago (1-3).CD1 molecules play an equally important role in the immune system, presenting lipid, glycolipid, and lipopeptide antigens to T and NKT cells (4-8). CD1 genes have long been thought to be as ancient as class I and II genes, based on several pieces of evidence, but thus far they have been described only in mammals (4, 9-11).That the CD1 system is related to MHC class I and II systems is clear, but the details of the evolutionary relationship are not (4 -8). By comparison of gene and protein sequences as well as 3D folds, CD1 is equally related to class I and II sequences and proteins. However, by intron͞exon structure and domain organization, CD1 is similar to class I genes and molecules, with a single transmembrane glycoprotein heavy chain of three extracellular domains that binds ␤ 2 -microglobulin (compared to class II genes and molecules, with two transmembrane glycoproteins, each of two extracellular domains). Conversely, CD1 molecules resemble class II molecules in terms of extensive intracellular trafficking, antigen loading in intracellu...

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Lymphoproliferation against foot-and-mouth disease (FMD) virus was examined using peripheral blood mononuclear cells from vaccinated cattle. Ten weeks after revaccination the optimum conditions for proliferation were obtained with 1 ~tg/ml of purified virus after 5 to 6 days in culture. This contrasted with the response at 20 months post-revaccination, when the response required less antigen and showed a peak response after 3 to 4 days in culture. Proliferation was specific for FMD virus, but was cross-reactive between serotypically distinct strains of the virus. The proliferative response to isolated virus proteins (VP) involved all three major capsid proteins (VP1, -2 and -3), although the proliferation of lymphocytes from heterotypically vaccinated cattle was due to VP3. Furthermore, the response induced by purified virus, chemically fixed virus and subunit virus particles was indistinguishable and thus it is likely that processing was required for the induction of proliferation. Together these data strongly suggest that FMD virus-induced lymphoproliferation is T cell-mediated and that VP3 may contain dominant, cross-reactive sequences.

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The role of T cells in immunity to foot-and-mouth disease virus is still poorly defined compared to that of the humoral response. In this paper we describe a systematic, longitudinal study on the cellular recognition of FMDV and its subunit protein VP1 by bovine peripheral blood T lymphocytes. Multiple vaccination with a single virus serotype induced a serotype crossreactive proliferative T cell repertoire that varied in magnitude between individual animals and with the serotype of the vaccine used. Primary proliferative T call responses of vaccinated and acutely infected cattle were weak relative to the magnitude of responses determined for the same animals after boosting. In contrast, the level of circulating antibody produced after both primary and secondary exposure to virus was good. Phenotypic analysis of lymphocytes from vaccinated or infected cattle showed a small increase in CD8 + T cells after infection compared to vaccination. However, in general the profiles of circulating lymphocytes elicited were similar. Thus, we were not able to use proliferative or phenotypic analyses to distinguish between vaccinated and convalescent cattle. T cell recognition of VP1 by multiply-vaccinated cattle was serotype-specific implying that the cross-reactive responses observed with whole virus may be attributed to proteins other than VP1. In contrast to other studies, immunization with recombinant VP1 induced only low levels of neutralizing antibody and failed to elicit profound proliferative responses or protection even after two immunizations.