TY - JOUR
T1 - Melanoma-specific CD4+ T cells recognize nonmutated HLA-DR-restricted tyrosinase epitopes
AU - Topalian, Suzanne L.
AU - Gonzales, Monica I.
AU - Parkhurst, Maria
AU - Li, Yong F.
AU - Southwood, Scott
AU - Sette, Alessandro
AU - Rosenberg, Steven A.
AU - Robbins, Paul F.
PY - 1996/5/1
Y1 - 1996/5/1
N2 - Tyrosinase was the first melanoma-associated antigen shown to be recognized by CD4+ T cells. In this study, we have identified two HLA- DRB1*0401-restricted peptides recognized by these T cells: Ty 56-70 and Ty 448-462. As with many of the MHC class I-restricted melanoma epitopes, both are nonmutated self peptides that have intermediate and weak MHC binding affinities, respectively. Mutated and truncated versions of these peptides were used to define their MHC binding anchor residues. Anchor residues were then modified to derive peptides with increased MHC binding affinities and T cell stimulatory properties. Ty 56-70 and Ty 448-462 enhance the list of immunogenic HLA-A2-, A24-, and B44-restricted tyrosinase peptides already described. Thus, tyrosinase provides a model for anti-melanoma vaccines in which a single molecule can generate multivalent immunization incorporating both CD4+ and CD8+ T cell responses.
AB - Tyrosinase was the first melanoma-associated antigen shown to be recognized by CD4+ T cells. In this study, we have identified two HLA- DRB1*0401-restricted peptides recognized by these T cells: Ty 56-70 and Ty 448-462. As with many of the MHC class I-restricted melanoma epitopes, both are nonmutated self peptides that have intermediate and weak MHC binding affinities, respectively. Mutated and truncated versions of these peptides were used to define their MHC binding anchor residues. Anchor residues were then modified to derive peptides with increased MHC binding affinities and T cell stimulatory properties. Ty 56-70 and Ty 448-462 enhance the list of immunogenic HLA-A2-, A24-, and B44-restricted tyrosinase peptides already described. Thus, tyrosinase provides a model for anti-melanoma vaccines in which a single molecule can generate multivalent immunization incorporating both CD4+ and CD8+ T cell responses.
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U2 - 10.1084/jem.183.5.1965
DO - 10.1084/jem.183.5.1965
M3 - Article
C2 - 8642306
AN - SCOPUS:0029979997
SN - 0022-1007
VL - 183
SP - 1965
EP - 1971
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -