Abstract

This grant application describes experiments that are aimed at achieving a detailed understanding of 1) T-cell recognition of antigens and 2) the developmental events that occur in the thymus during T-cell ontogeny. With these goals in mind, we are studying differences in the T-cell receptor (TCR) repertoire that occur between MHC-disparate strains of mice. We are also characterizing the T-cell receptor (TCR) repertoire to a class 2 alloantigen, I-Abm12, and to a class 1 alloantigen, Db.
The specific aims of this grant application are stated below.
Specific Aim 1 : To understand how the number of V beta 5- expressing T-cells is determined in B10 (H-2b) and B10.BR (H-2k) mice.
Specific Aim 2 : To continue our studies of the T-cell receptor repertoire to the class 2 alloantigen, I-Abm12.
Specific Aim 3 : To define the amino acid residues critical to the specificity of an alloreactive T-cell receptor using site directed mutagenesis.
Specific Aim 4 : To determine whether alloreactive T-cells can undergo selection based on their affinity for antigen (i.e. can T- cells undergo affinity maturation?)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI022259-04
Application #
3133162
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1985-09-01
Project End
1991-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
National Jewish Health
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206

  Publications

Ignatowicz, L; Kappler, J W; Marrack, P et al. (1994) Identification of two V beta 7-specific viral superantigens. J Immunol 152:65-71
Marrack, P; Hugo, P; McCormack, J et al. (1993) Death and T cells. Immunol Rev 133:119-29
Marrack, P; Winslow, G M; Choi, Y et al. (1993) The bacterial and mouse mammary tumor virus superantigens;two different families of proteins with the same functions. Immunol Rev 131:79-92
Hugo, P; Kappler, J W; Marrack, P C (1993) Positive selection of TcR alpha beta thymocytes: is cortical thymic epithelium an obligatory participant in the presentation of major histocompatibility complex protein? Immunol Rev 135:133-55
Pullen, A M; Choi, Y; Kushnir, E et al. (1992) The open reading frames in the 3' long terminal repeats of several mouse mammary tumor virus integrants encode V beta 3-specific superantigens. J Exp Med 175:41-7
Woodland, D L; Lund, F E; Happ, M P et al. (1991) Endogenous superantigen expression is controlled by mouse mammary tumor proviral loci. J Exp Med 174:1255-8
Pullen, A M; Bill, J; Kubo, R T et al. (1991) Analysis of the interaction site for the self superantigen Mls-1a on T cell receptor V beta. J Exp Med 173:1183-92
Herman, A; Croteau, G; Sekaly, R P et al. (1990) HLA-DR alleles differ in their ability to present staphylococcal enterotoxins to T cells. J Exp Med 172:709-17
Pullen, A M; Wade, T; Marrack, P et al. (1990) Identification of the region of T cell receptor beta chain that interacts with the self-superantigen MIs-1a. Cell 61:1365-74
Marrack, P; Blackman, M; Kushnir, E et al. (1990) The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells. J Exp Med 171:455-64

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