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PMID: 9239396 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Human histocompatibility leukocyte antigen-binding supermotifs predict broadly cross-reactive cytotoxic T lymphocyte responses in patients with acute hepatitis.

The Journal of clinical investigation ·Vol. 100 ·No. 3 ·1997-08-01 ·Pages 503-13

Bertoni R, Sidney J, Fowler P, Chesnut RW, Chisari FV, Sette A

Abstract

The present study was designed to determine if highly conserved hepatitis B virus (HBV)-derived peptides that bind multiple HLA class I alleles with high affinity are recognized as cytotoxic T lymphocyte (CTL) epitopes in acutely infected patients. Peripheral blood mononuclear cells from 67 patients with acute hepatitis B, and 12 patients convalescent from acute hepatitis B, were stimulated with three panels of peptides, each of which bind with high affinity to several class I alleles from the HLA-A2-, HLA-A3-, or HLA-B7-supertypes. In these patients, 8 of the 19 peptides tested were found to represent CTL epitopes recognized by two or more alleles in each supertype. Two sets of nested peptides were recognized in the context of alleles with completely unrelated peptide binding specificities. Finally, promiscuous recognition by the same CTL of a given peptide presented by target cells expressing different A2 subtypes was also commonly observed. In conclusion, several HBV-specific CTL epitopes, recognized by acutely infected or convalescent patients in the context of a wide range of HLA alleles have been identified. These results demonstrate the functional relevance of the supertype grouping of HLA class I molecules in a human viral disease setting. Furthermore, they represent a significant advance in the development of a totally synthetic vaccine to terminate chronic HBV infection and support the feasibility of a systematic approach to development of similar vaccines for prevention and treatment of other chronic viral infections.

MeSH Terms
Acute Disease Alleles Cytotoxicity, Immunologic HLA Antigens/immunology Hepatitis B/immunology,physiopathology Hepatitis B virus Histocompatibility Antigens Class I/genetics,immunology Humans Peptides/genetics,immunology Prognosis T-Lymphocytes/immunology Viral Proteins/immunology
Chemicals
HLA Antigens Histocompatibility Antigens Class I Peptides Viral Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bertoni R
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Sidney J
Fowler P
Chesnut R W
Chisari F V
Sette A
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119559
Published
1997-08-01
Pages
503-13
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508216
Subset
IM
Grants
NIAID NIH HHS · AI20001 · United States
NIAID NIH HHS · AI26626 · United States
NCRR NIH HHS · M01 RR00833 · United States
External Links
PubMed source DOI: 10.1172/JCI119559 PMC Full Text View journal details
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