Abstract

The specific aim of this project is to employ site-directed mutagenesis of the major human histocompatibility complex molecules (class I and class II), the restricting elements on the antigen presenting or target cell, in order to explore the relationship of their structures to their functions in the immune system, as well as to define the interaction of the class II antigen with the T cell protein CD4. In this study we will examine primarily the class I HLA antigen HLA-A2, and will also commence studies of the class II HLA antigen DRl.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020182-07
Application #
3129675
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Winkler, D G; Park, I; Kim, T et al. (1993) Phosphorylation of Ser-42 and Ser-59 in the N-terminal region of the tyrosine kinase p56lck. Proc Natl Acad Sci U S A 90:5176-80
Shin, J; Lee, S; Strominger, J L (1993) Translocation of TCR alpha chains into the lumen of the endoplasmic reticulum and their degradation. Science 259:1901-4
Latron, F; Pazmany, L; Morrison, J et al. (1992) A critical role for conserved residues in the cleft of HLA-A2 in presentation of a nonapeptide to T cells. Science 257:964-7
Morrison, J; Elvin, J; Latron, F et al. (1992) Identification of the nonamer peptide from influenza A matrix protein and the role of pockets of HLA-A2 in its recognition by cytotoxic T lymphocytes. Eur J Immunol 22:903-7
Strominger, J L; Santos-Aguado, J; Burakoff, S J et al. (1989) Mutants of HLA-A2 in the analysis of its structure and function. Cold Spring Harb Symp Quant Biol 54 Pt 1:361-3
Robbins, P A; Lettice, L A; Rota, P et al. (1989) Comparison between two peptide epitopes presented to cytotoxic T lymphocytes by HLA-A2. Evidence for discrete locations within HLA-A2. J Immunol 143:4098-103
Vega, M A; Strominger, J L (1989) Constitutive endocytosis of HLA class I antigens requires a specific portion of the intracytoplasmic tail that shares structural features with other endocytosed molecules. Proc Natl Acad Sci U S A 86:2688-92
McMichael, A J; Gotch, F M; Santos-Aguado, J et al. (1988) Effect of mutations and variations of HLA-A2 on recognition of a virus peptide epitope by cytotoxic T lymphocytes. Proc Natl Acad Sci U S A 85:9194-8
Barbosa, J A; Santos-Aguado, J; Mentzer, S J et al. (1987) Site-directed mutagenesis of class I HLA genes. Role of glycosylation in surface expression and functional recognition. J Exp Med 166:1329-50
Carroll, M C; Katzman, P; Alicot, E M et al. (1987) Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes. Proc Natl Acad Sci U S A 84:8535-9

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