PMID- 7536421
OWN - NLM
STAT- MEDLINE
DCOM- 19950523
LR  - 20071115
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 9
IP  - 2
DP  - 1995 Feb
TI  - Induction of a primary human cytotoxic T-lymphocyte response against a novel 
      conserved epitope in a functional sequence of HIV-1 reverse transcriptase.
PG  - 121-7
AB  - OBJECTIVE: To identify novel major histocompatibility complex (MHC) class 
      I-restricted cytotoxic T-lymphocyte (CTL) epitopes conserved in HIV-1. METHODS: 
      Potential conserved CTL epitopes were selected using a predictive computer 
      algorithm based on a human leukocyte antigen (HLA)-A*0201 peptide-binding motif 
      and tested for actual binding to the human processing defective cell line 174.CEM 
      T2 (T2). Hence, the amino-acid sequences of 14 full-length sequenced HIV-1 
      strains were analysed. An in vitro primary peptide-specific human CTL response 
      was induced with responding lymphocytes of an HIV-1-seronegative donor. 
      Responding T cells were cloned by limiting dilution and tested for their ability 
      to recognize naturally processed antigen in a 51Cr-release assay using 
      recombinant vaccinia-HIV protein-infected B-lymphoblastoid cells (B-LCL) as 
      target cells. RESULTS: The analysis of peptides bearing the HLA-A*0201 motif for 
      conservation resulted in one peptide of Env, three of Gag and 12 of Pol. Only 
      Gag340-348, Pol83-92, Pol267-277 and Pol960-968 showed binding properties to T2 
      comparable with those of known CTL epitopes Gag76-84 SLYNTVATL and Pol468-476 
      ILKEPVHGV. A successful primary MHC class I-restricted CTL response was induced 
      against Pol468-476 and Pol267-277 VLDVGDAYFSV, a peptide in a functional sequence 
      of reverse transcriptase (RT). The resulting CD8+ CTL clones were 
      peptide-specific and able to specifically lyse recombinant vaccinia-HIV-1 
      RT-infected HLA-A*0201-matched B-LCL. CONCLUSION: The method used to screen 
      proteins sequences for potential CTL epitopes, test selected peptides for binding 
      to MHC class I and induction of an in vitro primary response against optimal 
      binding peptides resulted in the identification of at least one novel conserved 
      CTL epitope. The novel epitope is located in an area crucial for RT activity. 
      This study demonstrates the feasibility of identifying highly conserved 
      HIV-1-derived peptides capable of eliciting novel anti-HIV-1 CTL responses.
FAU - van der Burg, S H
AU  - van der Burg SH
AD  - Department of Immunohaematology, University Hospital, Leiden, The Netherlands.
FAU - Klein, M R
AU  - Klein MR
FAU - van de Velde, C J
AU  - van de Velde CJ
FAU - Kast, W M
AU  - Kast WM
FAU - Miedema, F
AU  - Miedema F
FAU - Melief, C J
AU  - Melief CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Epitopes)
RN  - 0 (HLA-A Antigens)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
RN  - EC 2.7.7.49 (RNA-Directed DNA Polymerase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cell Line
MH  - Conserved Sequence
MH  - Epitopes/immunology
MH  - HIV Reverse Transcriptase
MH  - HIV-1/*enzymology
MH  - HLA-A Antigens/chemistry/*immunology
MH  - Humans
MH  - Lymphocyte Activation
MH  - Molecular Sequence Data
MH  - RNA-Directed DNA Polymerase/chemistry/*immunology
MH  - Sequence Alignment
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 1995/02/01 00:00
MHDA- 1995/02/01 00:01
CRDT- 1995/02/01 00:00
PHST- 1995/02/01 00:00 [pubmed]
PHST- 1995/02/01 00:01 [medline]
PHST- 1995/02/01 00:00 [entrez]
PST - ppublish
SO  - AIDS. 1995 Feb;9(2):121-7.