Class I HLA antigens present an array of peptides for recognition by cytotoxic T lymphocytes (CTL). Under normal circumstances these peptides derive from naturally synthesized host proteins, and are tolerated by the immune system. However, during viral infection the pool of peptides presented by class I MHC molecules shifts to reflect inappropriate foreign protein synthesis, and in this way marks these cells for destruction. The objective of the studies proposed here are to: (1) determine the peptide binding motifs for HLA class I molecules as a means to predict HIV-1 restricted T cell epitopes, (2) test CTL from HIV-1+ patients for recognition of these peptides as a function of time and clinical status, and (3) isolate and characterize anti-peptide CTL clones to study virus- specific recognition and immunity and utilize this information to engineer analogs able to elicit an enhanced immune response against HIV-1. This experimental approach uses the polymerase chain reaction (PCR) to amplify HLA class I genes for expression in insect cells from a baculoviral vector. Recombinant proteins will be used to screen a synthetic peptide library to determine allele-specific peptide binding motifs, and the resultant peptides will be synthesized and used to stimulate T cells from HIV-1 seropositive individuals. CTL generated in this manner will be tested for recognition of cells transfected with the appropriate class I gene and individual HIV-1 genes. Predicting and testing peptide sequences to elicit antiviral immune responses would provide better understanding of immunity to AIDS, with applications for other viral, malignant, and autoimmune disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29AI036712-01A2
Application #
2073167
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1995-06-15
Project End
2000-05-31
Budget Start
1995-06-15
Budget End
1996-05-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Arizona
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721