Abstract

This grant proposal seeks to better understand the positive and negative selective forces which shape the T cell repertoire and the general focus of the grant is on the characterization of non-MHC genes which influence thymic selection. We plan to continue characterizing a gene, Et-1, that is absolutely required for the clonal deletion of I-E reactive cells and whose corresponding gene product is likely a member of the M1s-family of antigens. The molecular relationship between Et-1 and the endogenous viral genome, Mtv-9, will be determined. A second I-E co-tolerogen, Et- 2, present in the DBA/2 strain will be characterized with an emphasis on determining whether or not it is related to endogenous viral sequences. To study the effects of non-MHC genes on positive selection, we will carry out an analysis of the background (non-MHC) genes which determine the frequency of V-beta-11+/CD8+T cells. Finally, we will study the effects of background genes on the positive selection of a single T cell receptor in a T cell receptor transgenic mouse.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022259-08
Application #
3133168
Study Section
Immunobiology Study Section (IMB)
Project Start
1985-09-01
Project End
1993-03-31
Budget Start
1992-09-01
Budget End
1993-03-31
Support Year
8
Fiscal Year
1992
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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