T-Cell Stimulating Antigen Genes in Tumor Cells

Institution:	University of California, Berkeley
Investigator(s):	Nilabh Shastri, Ph.D.
Award Cycle:	1994 (Cycle 3)	Grant #: 3RT-0289	Award: $362,814
Subject Area:	Cancer
Award Type:	Research Project Awards

Abstracts

Initial Award Abstract

This project aims to identify the antigen genes that are expressed in normal as well as tumor cells and are recognized by T-cells as peptide/MHC complexes. We are identifying and isolating these genes using our unique expression cloning strategies for both CD4+ and CD8+ T-cell defined antigens. Towards this end we have generated a panel of lacZ inducible T cell hybrids that recognize unknown antigens expressed by B6 spleen cells, mouse tumors and the bacterial pathogen listeria monocytogenes. With two of these T-cells (bmlBZ19.4, and LMZ30.4) used as a single cell probes, we have isolated a cDNA clone from mouse B6 spleen cell and listeria monocytogenes DNA libraries respectively. These results have established expression cloning strategies for identifying unknown T-cell stimulating antigens and have provided knowledge of the peptides and their donor proteins that elicit T-cell immunity. We are currently extending these results to identify the unknown antigen genes recognized by the other T-cells in our panel. We expect the results will allow us to (a) establish the protein sources for peptide/MHC complex expressed on the antigen presenting cell surface, (b) determine the role of these antigenic peptides in the induction of specific T-cell immunity.

Publications

LacZ inducible, antigen/MHC specific T-cell hybrids
Periodical: International Immunology			Index Medicus:
Authors: Sanderson S, Shastri N				ART
Yr: 1994	Vol: 6	Nbr: 3	Abs:	Pg: 369-376

Expression of endogenous peptide/MHC class II complexes derived from invariant chain/antigen fusion proteins
Periodical: Proceedings of the National Academy of Sciences of the United States of America			Index Medicus:
Authors: Sanderson S, Frauwirth K, Shastri N				ART
Yr: 1995	Vol: 92	Nbr: 16	Abs:	Pg: 7217-7221

Presentation without processing of endogenous precursors in the MHC class I antigen processing pathway
Periodical: Journal of Biological Chemistry			Index Medicus:
Authors: Buchholz D, Scott P, Shastri N				ART
Yr: 1995	Vol: 270	Nbr: 12	Abs:	Pg: 6515-6522

Major histocompatibility class I molecules present cryptic translation products to T-cells
Periodical: Journal of Biological Chemistry			Index Medicus:
Authors: Shastri N, Nguyen V, Gonzalez F				ART
Yr: 1995	Vol: 270	Nbr: 3	Abs:	Pg: 1088-1091

The roles of MHC class I molecules in the generation of endogenous peptide/MHC complexes
Periodical: Journal of Immunology			Index Medicus:
Authors: Malarkannan S, Goth S, Buchholz DR, Shastri N				ART
Yr: 1995	Vol: 154	Nbr: 12	Abs:	Pg: 585-598

Single T-cell probes for antigen/MHC expression
Periodical: Current Opinion in Immunology			Index Medicus:
Authors: Shastri N				ART
Yr: 1995	Vol: 7	Nbr: 2	Abs:	Pg: 258-262

LacZ inducible, antigen/MHC specific T-cell hybrids
Periodical: International Immunology			Index Medicus:
Authors: Sanderson S, Shastri N				ART
Yr: 1994	Vol: 6	Nbr: 3	Abs:	Pg: 369-376

Expression of endogenous peptide/MHC class II complexes derived from invariant chain/antigen fusion proteins
Periodical: Proceedings of the National Academy of Sciences of the United States of America			Index Medicus:
Authors: Sanderson S, Frauwirth K, Shastri N				ART
Yr: 1995	Vol: 92	Nbr: 16	Abs:	Pg: 7217-7221

Presentation without processing of endogenous precursors in the MHC class I antigen processing pathway
Periodical: Journal of Biological Chemistry			Index Medicus:
Authors: Buchholz D, Scott P, Shastri N				ART
Yr: 1995	Vol: 270	Nbr: 12	Abs:	Pg: 6515-6522

Major histocompatibility class I molecules present cryptic translation products to T-cells
Periodical: Journal of Biological Chemistry			Index Medicus:
Authors: Shastri N, Nguyen V, Gonzalez F				ART
Yr: 1995	Vol: 270	Nbr: 3	Abs:	Pg: 1088-1091

The roles of MHC class I molecules in the generation of endogenous peptide/MHC complexes
Periodical: Journal of Immunology			Index Medicus:
Authors: Malarkannan S, Goth S, Buchholz DR, Shastri N				ART
Yr: 1995	Vol: 154	Nbr: 12	Abs:	Pg: 585-598

Single T-cell probes for antigen/MHC expression
Periodical: Current Opinion in Immunology			Index Medicus:
Authors: Shastri N				ART
Yr: 1995	Vol: 7	Nbr: 2	Abs:	Pg: 258-262