The major histocompatibility complex (Mhc) is a family of genes whose function is to provide context for the recognition of foreign antigens by T lymphocytes. One of the distinguishing features of the Mhc is its polymorphism, that is, the occurrence in natural populations of large numbers of alleles at some of the Mhc loci, all at appreciable frequencies. The overall goal of the proposed research is to determine how the Mhc polymorphism arises and to elucidate its biological significance. The proposed project will attempt to answer questions such as: How fast do Mhc genes diversify? What mechanisms are involved in this diversification? What is the origin of the polymorphic Mhc loci? What role does the t complex (a set of linked loci affecting differentiation) play in the generation of the Mhc polymorphism? To what degree does the polymorphism correlate with the adaptiveness of a species to its environment? Answers to these questions will be sought by extracting DNA from populations of wild mice and mole-rats, and studying it using methods of molecular biology. The study should contribute to three areas of human knowledge. In immunology, the results might provide a clue to understanding why T lymphocytes need to recognize nonself in the context of self. In general biology, the study of polymorphism should provide information on how a species copes with its environment, in particular the invading parasites. In evolutionary biology, the data should shed light on how speciation begins. Although the studies will be carried out on rodents, it is hoped that they will be directly applicable to humans who, like mice, possess a highly polymorphic Mhc.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023667-03
Application #
3135951
Study Section
Immunobiology Study Section (IMB)
Project Start
1986-09-01
Project End
1991-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33101
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Vincek, V; Klein, D; Graser, R T et al. (1995) Molecular cloning of major histocompatibility complex class II B gene cDNA from the Bengalese finch Lonchura striata. Immunogenetics 42:262-7
Trtkova, K; Mayer, W E; O'Huigin, C et al. (1995) Mhc-DRB genes and the origin of New World monkeys. Mol Phylogenet Evol 4:408-19
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Mayer, W E; O'hUigin, C; Klein, J (1993) Resolution of the HLA-DRB6 puzzle: a case of grafting a de novo-generated exon on an existing gene. Proc Natl Acad Sci U S A 90:10720-4
Klein, J; Satta, Y; Takahata, N et al. (1993) Trans-specific Mhc polymorphism and the origin of species in primates. J Med Primatol 22:57-64
Sultmann, H; Mayer, W E; Figueroa, F et al. (1993) Zebrafish Mhc class II alpha chain-encoding genes: polymorphism, expression, and function. Immunogenetics 38:408-20
Ono, H; O'hUigin, C; Tichy, H et al. (1993) Major-histocompatibility-complex variation in two species of cichlid fishes from Lake Malawi. Mol Biol Evol 10:1060-72

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