Abstract
CTL reactivity to the epitope MART-1((27-35)) of the melanoma (self) antigen MART-1/melan A is frequently observed in tumor-infiltrating lymphocytes and may be readily elicited from the peripheral blood of melanoma patients that express HLA-A*0201. Available data suggest that these observations contrast with those made for other HLA-A*0201-presented melanoma self antigens regrading the regularity of observed CTL responses. Based of preliminary findings, we hypothesized that the CTL response to MART- 1 might be augmented in part by T cell encounters with peptides derived from sources other than MART-1, which show sequence similarity to MART-1((27- 35)). To test this idea, a protein database search for potential MART-1 epitope mimics was done using criteria developed from analyses of effector recognition of singly-substituted peptide analogues of MART-1((27-35)). Synthetic peptides were made for a portion of the sequences retrieve; 12/40 peptides tested were able to sensitive target cells for lysis by one or more ant-MART-1 effectors. The peptides recognized corresponds to sequences occurring in a variety of proteins of viral, bacterial, and human (self) origin. One peptide derives from glycoprotein C of the common pathogen HSV- 1; cells infected with recombinant vaccinia virus encoding native glycoprotein C were lysed by anti-MART-1 effectors. Our results overall indicate that sequences conforming to the A2.1 binding motif and possessing features essential to recognition by anti-MART-1 CTL, occur frequently in proteins. These findings further suggest that T cells might encounter a variety of such sequences in vivo, and that epitope mimicry may play a role in modulating the CTL response to MART-1((27-35)).
| Original language | English |
|---|---|
| Pages (from-to) | 647-657 |
| Number of pages | 11 |
| Journal | Journal of Experimental Medicine |
| Volume | 184 |
| Issue number | 2 |
| Publication status | Published - Aug 1 1996 |
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ASJC Scopus subject areas
- Immunology
Cite this
Identification of epitope mimics recognized by CTL reactive to the melanoma/melanocyte-derived peptide MART-1((27-35)). / Loftus, Douglas J.; Castelli, Chiara; Clay, Timothy M.; Squarcina, Paola; Marincola, Francesco M.; Nishimura, Michael I.; Parmiani, Giorgio; Appella, Ettore; Rivoltini, Licia.
In: Journal of Experimental Medicine, Vol. 184, No. 2, 01.08.1996, p. 647-657.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identification of epitope mimics recognized by CTL reactive to the melanoma/melanocyte-derived peptide MART-1((27-35))
AU - Loftus, Douglas J.
AU - Castelli, Chiara
AU - Clay, Timothy M.
AU - Squarcina, Paola
AU - Marincola, Francesco M.
AU - Nishimura, Michael I.
AU - Parmiani, Giorgio
AU - Appella, Ettore
AU - Rivoltini, Licia
PY - 1996/8/1
Y1 - 1996/8/1
N2 - CTL reactivity to the epitope MART-1((27-35)) of the melanoma (self) antigen MART-1/melan A is frequently observed in tumor-infiltrating lymphocytes and may be readily elicited from the peripheral blood of melanoma patients that express HLA-A*0201. Available data suggest that these observations contrast with those made for other HLA-A*0201-presented melanoma self antigens regrading the regularity of observed CTL responses. Based of preliminary findings, we hypothesized that the CTL response to MART- 1 might be augmented in part by T cell encounters with peptides derived from sources other than MART-1, which show sequence similarity to MART-1((27- 35)). To test this idea, a protein database search for potential MART-1 epitope mimics was done using criteria developed from analyses of effector recognition of singly-substituted peptide analogues of MART-1((27-35)). Synthetic peptides were made for a portion of the sequences retrieve; 12/40 peptides tested were able to sensitive target cells for lysis by one or more ant-MART-1 effectors. The peptides recognized corresponds to sequences occurring in a variety of proteins of viral, bacterial, and human (self) origin. One peptide derives from glycoprotein C of the common pathogen HSV- 1; cells infected with recombinant vaccinia virus encoding native glycoprotein C were lysed by anti-MART-1 effectors. Our results overall indicate that sequences conforming to the A2.1 binding motif and possessing features essential to recognition by anti-MART-1 CTL, occur frequently in proteins. These findings further suggest that T cells might encounter a variety of such sequences in vivo, and that epitope mimicry may play a role in modulating the CTL response to MART-1((27-35)).
AB - CTL reactivity to the epitope MART-1((27-35)) of the melanoma (self) antigen MART-1/melan A is frequently observed in tumor-infiltrating lymphocytes and may be readily elicited from the peripheral blood of melanoma patients that express HLA-A*0201. Available data suggest that these observations contrast with those made for other HLA-A*0201-presented melanoma self antigens regrading the regularity of observed CTL responses. Based of preliminary findings, we hypothesized that the CTL response to MART- 1 might be augmented in part by T cell encounters with peptides derived from sources other than MART-1, which show sequence similarity to MART-1((27- 35)). To test this idea, a protein database search for potential MART-1 epitope mimics was done using criteria developed from analyses of effector recognition of singly-substituted peptide analogues of MART-1((27-35)). Synthetic peptides were made for a portion of the sequences retrieve; 12/40 peptides tested were able to sensitive target cells for lysis by one or more ant-MART-1 effectors. The peptides recognized corresponds to sequences occurring in a variety of proteins of viral, bacterial, and human (self) origin. One peptide derives from glycoprotein C of the common pathogen HSV- 1; cells infected with recombinant vaccinia virus encoding native glycoprotein C were lysed by anti-MART-1 effectors. Our results overall indicate that sequences conforming to the A2.1 binding motif and possessing features essential to recognition by anti-MART-1 CTL, occur frequently in proteins. These findings further suggest that T cells might encounter a variety of such sequences in vivo, and that epitope mimicry may play a role in modulating the CTL response to MART-1((27-35)).
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M3 - Article
C2 - 8760818
AN - SCOPUS:0029788301
VL - 184
SP - 647
EP - 657
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 2
ER -