Isolation of an endogenously processed immunodominant viral peptide from the class I H–2Kb molecule

Bleek, Grada M. van; Nathenson, Stanley G.

doi:10.1038/348213a0

Cited by 659 publications

(334 citation statements)

References 45 publications

Supporting

Mentioning

318

Contrasting

Order By: Relevance

“…In addition to allowing a precise assessment of the effects of sequence variation on recognition by CTL, the determination of minimum CTL epitopes may also facilitate the identification of alhle-specific motifs. The minimum epitopes identified here of eight and nine aa for the HLA-B8-and B14-restricted gp41 epitopes are consistent with the recent characterization of naturally processed peptides of eight or nine aa in both mouse and humans (45)(46)(47)(48)(49)(50) and the crystalline structure of the peptide binding pocket of the HLA-B27 molecule (51). The minimum epitopes defined in this study using serial truncations of synthetic peptides may well correspond to the naturally processed peptide, consistent with the ability of the octamer HLA-B8-restricted gp41 epitope to sensitize target cells at picomolar concentrations.…”

Section: Discussionsupporting

confidence: 64%

Identification of overlapping HLA class I-restricted cytotoxic T cell epitopes in a conserved region of the human immunodeficiency virus type 1 envelope glycoprotein: definition of minimum epitopes and analysis of the effects of sequence variation.

Johnson

Trocha

Buchanan

et al. 1992

The Journal of Experimental Medicine

121

View full text Add to dashboard Cite

Although the immunologic basis of protective immunity in human immunodeficiency virus type 1 (HIV-1) infection has not yet been defined, virus-specific cytotoxic T lymphocytes (CTL) are likely to be an important host defense and may be a critical feature of an effective vaccine. These observations, along with the inclusion of the HIV-1 envelope in the majority of vaccine candidates presently in clinical trials, underscore the importance of the precise characterization of the cellular immune responses to this protein. Although humoral immune responses to the envelope protein have been extensively characterized, relatively little information is available regarding the envelope epitopes recognized by virus-specific CTL and the effects of sequence variation within these epitopes. Here we report the identification of two overlapping CTL epitopes in a highly conserved region of the HIV-1 transmembrane envelope protein, gp41, using CTL clones derived from two seropositive subjects. An eight-amino acid peptide was defined as the minimum epitope recognized by HLA-B8-restricted CTL derived from one subject, and in a second subject, an overlapping nine-amino acid peptide was identified as the minimal epitope for HLA-B14-restricted CTL clones. Selected single amino acid substitutions representing those found in naturally occurring HIV-1 isolates resulted in partial to complete loss of recognition of these epitopes. These data indicate the presence of a highly conserved region in the HIV-1 envelope glycoprotein that is immunogenic for CTL responses. In addition, they suggest that natural sequence variation may lead to escape from immune detection by HIV-1-specific CTL. Since the region containing these epitopes has been previously shown to contain an immunodominant B cell epitope and also overlaps with a major histocompatibility complex class II T cell epitope recognized by CD4+ CTL from HIV-1 rgp160 vaccine recipients, it may be particularly important for HIV-1 vaccine development. Finally, the identification of minimal CTL epitopes presented by class I HLA molecules should facilitate the definition of allele-specific motifs.

show abstract

Section: Discussionsupporting

confidence: 64%

Identification of overlapping HLA class I-restricted cytotoxic T cell epitopes in a conserved region of the human immunodeficiency virus type 1 envelope glycoprotein: definition of minimum epitopes and analysis of the effects of sequence variation.

Johnson

Trocha

Buchanan

et al. 1992

The Journal of Experimental Medicine

121

View full text Add to dashboard Cite

show abstract

“…injection of 5 mg OVA with 100 g anti-CD40 mAb or 100 g control rat Ig. At the indicated times, lymphocytes were isolated and OVA-specific CD8 T cells were detected using H-2K b tetramers containing the OVA protein-derived peptide SIINFEKL (32) or the vesicular stomatitis virus N protein-derived peptide RGYVYQGL. MHC tetramers were produced essentially as previously described (33,34).…”

Section: Detection Of Ova-specific Primary and Memory Cd8 T Cells Witmentioning

confidence: 99%

Soluble Antigen and CD40 Triggering Are Sufficient to Induce Primary and Memory Cytotoxic T Cells

Lefrançois

Altman

Williams

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

The signals directing induction of tolerance rather than immunity are largely unknown. The CD8 T cell response to soluble Ags generally results in deletional tolerance following transient, costimulation-dependent activation. We demonstrated that CD40 signaling reversed the outcome of this response. Adoptive transfer of OVA-specific CD8 T cells followed by soluble OVA immunization resulted in induction of lytic activity and optimal clonal expansion only when CD40 was triggered via an agonistic mAb. Activation of CD8 T cells by CD40 signaling was indirect, because CD40 expression by host cells was required. CD40 signaling along with soluble Ag immunization also induced expansion of secondary lymphoid and intestinal mucosal endogenous OVA-specific CD8 T cells as detected by MHC tetramer reactivity. When CD40 activation was included, long-lived secondary lymphoid and mucosal memory CD8 cells were generated from adoptively transferred and endogenous CD8 T cells. Mucosal and peripheral CD8 memory cells exhibited constitutive Ag-specific lytic activity, with mucosal memory cells being 10-fold more lytic than splenic or lymph node memory cells. These results demonstrated that CD40 signaling during a response to a poorly immunogenic soluble Ag was necessary and sufficient for CTL and memory T cell induction.

show abstract

“…More than the half of the positive peptides were identified as positives in both assays, but many were positive only in one assay. We have used 24 aa long HIV gag peptides which should be compared with reservation with those of 15 aa long peptides screened in the in vitro assembly assay by Elvin et al In vivo presented "natural" peptides are 8-9 aa long [33,[36][37][38]. The suboptimal 24 aa length of our peptides may explain the observation that none of the HIV-1 gag peptides had as high capacity to enhance class I expression as the shorter control influenza peptides (2-2.9 times and 3.9-5.6 times elevation, respectively; Table 1).…”

Section: The 174/t2 Cellsmentioning

confidence: 99%

Assessment of major histocompatibility complex class I interaction with Epstein‐Barr virus and human immunodeficiency virus peptides by elevation of membrane H‐2 and HLA in peptide loading‐deficient cells

et al. 1992

View full text Add to dashboard Cite

Earlier findings indicate that peptides can affect the expression of major histocompatibility complex (MHC) class I molecules on the surface of cells with defective peptide loading mechanism. We have used peptide induced increase of class I antigen expression to assess peptide interaction with MHC class I molecules. A panel of 41 overlapping synthetic peptides derived from the human immunodeficiency virus-1 (HIV-1) gag protein and 33 nonoverlapping peptides from Epstein-Barr virus (EBV) proteins EBNA-1, 2, 3, 4, 5 , 6, LMP, BZLF2, BILF2, BSLF2, BALF4 and BcLFl was assessed for the ability to enhance the expression of HLA-A2.1, H-2Db, Kh and Dd on the murine RMA-S and human 721.174/T2 (. 174/T2) lines by indirect immunofluorescence. Considering doubling of the fluorescence intensity in the peptide-treated samples as positivity, 6 of 39 HIVand 1 of 32 EBVpeptides were found to bind to A2.1,6 of 39 HIVgag and 7 of 16 EBVpeptides to Dh, 8 of 39 HIVgag and 5 of 16 EBV peptides to Kb and 2 of 39 HIV gag and 1 of 17 EBV peptides to Dd. The sensitivity of the method is comparable to the in vitro class I assembly assay with conformation-dependent monoclonal antibody and is more discriminating than the solid-phase assay. Due to its simplicity this method can also serve for testing large peptide panels for binding capacity to various class I molecules. Moreover, the method provides information about the relevance of in vitro tests for class I assembly in living cells.

show abstract

Isolation of an endogenously processed immunodominant viral peptide from the class I H–2Kb molecule

Cited by 659 publications

References 45 publications

Identification of overlapping HLA class I-restricted cytotoxic T cell epitopes in a conserved region of the human immunodeficiency virus type 1 envelope glycoprotein: definition of minimum epitopes and analysis of the effects of sequence variation.

Identification of overlapping HLA class I-restricted cytotoxic T cell epitopes in a conserved region of the human immunodeficiency virus type 1 envelope glycoprotein: definition of minimum epitopes and analysis of the effects of sequence variation.

Soluble Antigen and CD40 Triggering Are Sufficient to Induce Primary and Memory Cytotoxic T Cells

Assessment of major histocompatibility complex class I interaction with Epstein‐Barr virus and human immunodeficiency virus peptides by elevation of membrane H‐2 and HLA in peptide loading‐deficient cells

Contact Info

Product

Resources

About