Abstract
HLA-A0201-restricted melanoma-reactive CTL responses have been extensively studied; this allele is widely expressed among Caucasians, a group at risk for melanoma. We observed an unexpectedly high frequency ( 20%) of non-HLA-A0201 allelic variants (including 0205, "0204 and 0202) in a group of Italian melanoma patients. In the present study we analyzed peptide presentation by different HLA-A2 subtypes using melanoma-derived epitopes MART-l(27-35) , G9-154 and G9-280, and Flu-Ml(58-66). These peptides bound to most of the subtypes tested with IC50 values less than 500 nM, though instances of very poor binding were also noted. HLA-A0201restricted CTL displayed a limited ability to recognize peptide-pulsed EBV-B cell lines expressing different subtype molecules. Patterns of recognition varied with the peptides and effectors tested. In immunogenicity experiments, only anti-G9-280 CTL could be generated from PBL of 3β HLA-A0205 melanoma patients by in vitro peptide sensitization, while only anti-FluMl(58-66) CTL were induced in 2/2 HLA-A0202 subjects. Anti-G9-280 specific CTL recognized HLA-A0205 melanoma cells, indicating that this epitope is endogenously presented. These data imply .the necessity of subtyping patients undergoing peptide-based protocols and underline the need for additional studies of melanoma-directed T cell responses among patients expressing non-HLAA0201 subtypes.
| Original language | English |
|---|---|
| Journal | FASEB Journal |
| Volume | 10 |
| Issue number | 6 |
| Publication status | Published - 1996 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Cell Biology
Cite this
Binding, presentation and immunogenicity of peptides derived from melanoma antigens MART1 and GPZOO by HLA-A2 subtypes. / Rivoltini, L.; Loftus, D. J.; Barracchini, K.; Arienti, F.; Mazzocchi, A.; Squarcina, P.; Biddison, W. E.; Appella, E.; Parmiani, G.; Marincola, F. M.
In: FASEB Journal, Vol. 10, No. 6, 1996.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Binding, presentation and immunogenicity of peptides derived from melanoma antigens MART1 and GPZOO by HLA-A2 subtypes
AU - Rivoltini, L.
AU - Loftus, D. J.
AU - Barracchini, K.
AU - Arienti, F.
AU - Mazzocchi, A.
AU - Squarcina, P.
AU - Biddison, W. E.
AU - Appella, E.
AU - Parmiani, G.
AU - Marincola, F. M.
PY - 1996
Y1 - 1996
N2 - HLA-A0201-restricted melanoma-reactive CTL responses have been extensively studied; this allele is widely expressed among Caucasians, a group at risk for melanoma. We observed an unexpectedly high frequency ( 20%) of non-HLA-A0201 allelic variants (including 0205, "0204 and 0202) in a group of Italian melanoma patients. In the present study we analyzed peptide presentation by different HLA-A2 subtypes using melanoma-derived epitopes MART-l(27-35) , G9-154 and G9-280, and Flu-Ml(58-66). These peptides bound to most of the subtypes tested with IC50 values less than 500 nM, though instances of very poor binding were also noted. HLA-A0201restricted CTL displayed a limited ability to recognize peptide-pulsed EBV-B cell lines expressing different subtype molecules. Patterns of recognition varied with the peptides and effectors tested. In immunogenicity experiments, only anti-G9-280 CTL could be generated from PBL of 3β HLA-A0205 melanoma patients by in vitro peptide sensitization, while only anti-FluMl(58-66) CTL were induced in 2/2 HLA-A0202 subjects. Anti-G9-280 specific CTL recognized HLA-A0205 melanoma cells, indicating that this epitope is endogenously presented. These data imply .the necessity of subtyping patients undergoing peptide-based protocols and underline the need for additional studies of melanoma-directed T cell responses among patients expressing non-HLAA0201 subtypes.
AB - HLA-A0201-restricted melanoma-reactive CTL responses have been extensively studied; this allele is widely expressed among Caucasians, a group at risk for melanoma. We observed an unexpectedly high frequency ( 20%) of non-HLA-A0201 allelic variants (including 0205, "0204 and 0202) in a group of Italian melanoma patients. In the present study we analyzed peptide presentation by different HLA-A2 subtypes using melanoma-derived epitopes MART-l(27-35) , G9-154 and G9-280, and Flu-Ml(58-66). These peptides bound to most of the subtypes tested with IC50 values less than 500 nM, though instances of very poor binding were also noted. HLA-A0201restricted CTL displayed a limited ability to recognize peptide-pulsed EBV-B cell lines expressing different subtype molecules. Patterns of recognition varied with the peptides and effectors tested. In immunogenicity experiments, only anti-G9-280 CTL could be generated from PBL of 3β HLA-A0205 melanoma patients by in vitro peptide sensitization, while only anti-FluMl(58-66) CTL were induced in 2/2 HLA-A0202 subjects. Anti-G9-280 specific CTL recognized HLA-A0205 melanoma cells, indicating that this epitope is endogenously presented. These data imply .the necessity of subtyping patients undergoing peptide-based protocols and underline the need for additional studies of melanoma-directed T cell responses among patients expressing non-HLAA0201 subtypes.
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M3 - Article
VL - 10
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 6
ER -