Mixed Lymphocyte Reactivity in Chimpanzees II. Family Studies and Identification of D Locus Antigens*

The usefulness of nonhuman primates in immunologically relevant research has until now been limited by difficulties in characterizing the major histocompatibility (MHC) gene products of these species. We have now biochemically characterized the MHC-encoded class I molecules from four different species of nonhuman primates using antibodies directed against human MHC class I structures and one-dimensional isoelectric focusing (1-D IEF). We demonstrated the functional relevancy of this technique of MHC typing by generating virus-specific cytotoxic T cells and assaying their cytotoxic activity against a panel of virus-transformed cells that expressed the same or differing class I structures. Only virus-infected cell lines expressing MHC class I antigens identical to those of the cytotoxic T lymphocyte population were lysed. This simple method of MHC class I typing using 1-D IEF will be useful in immunological research involving nonhuman primates and in nonhuman primate colony management.

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Major histocompatibility complex class I molecules of nonhuman primates

Watkins

Kannagi

Stone

et al. 1988

Eur J Immunol

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The major histocompatibility complex of primates

et al. 1987

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The chimpanzee major histocompatibility complex class II DR subregion contains an unexpectedly high number of beta-chain genes

et al. 1990

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The major histocompatibility complex (MHC) class II DR subregion of the chimpanzee was studied by restriction fragment length polymorphism (RFLP) analysis. Genomic DNA obtained from a panel of 94 chimpanzees was digested with the restriction enzyme Taq I and hybridized with an HLA-DR beta probe specific for the 3' untranslated (UT) region. Such a screening revealed the existence of 14 distinct DRB/Taq I gene-associated fragments allowing the definition of 11 haplotypes. Segregation studies proved that the number of chimpanzee class II DRB/Taq I fragments is not constant and varies from three to six depending on the haplotype. Comparison of these data with a human reference panel manifested that some MHC DRB/Taq I fragments are shared by man and chimpanzee. Moreover, the number of HLA-DRB/Taq I gene-associated fragments detected in a panel of homozygous typing cells varies from one to three and corresponds with the number of HLA-DRB genes present for most haplotypes. However, a discrepancy is observed for the HLA-DR4, -DR7, and -DR9 haplotypes since a fourth HLA-DRB pseudogene present within these haplotypes lacks its 3' UT region and thus is not detected with the probe used. These results suggest that chimpanzees have a higher maximum number of DRB genes per haplotype than man. As a consequence, some chimpanzee haplotypes must show a dissimilar organization of the MHC DR subregion compared to their human equivalents. The implications of these findings are discussed in the context of the trans-species theory of MHC polymorphism.

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Mixed Lymphocyte Reactivity in Chimpanzees II. Family Studies and Identification of D Locus Antigens*

Cited by 11 publications

References 12 publications

Major histocompatibility complex class I molecules of nonhuman primates

Major histocompatibility complex class I molecules of nonhuman primates

The major histocompatibility complex of primates

The chimpanzee major histocompatibility complex class II DR subregion contains an unexpectedly high number of beta-chain genes

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