T-cell recognition of human melanoma antigens - PubMed (original) (raw)

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T-cell recognition of human melanoma antigens

Y Kawakami et al. J Immunother Emphasis Tumor Immunol. 1993 Aug.

Abstract

The adoptive transfer of tumor-infiltrating lymphocytes (TILs) with interleukin-2 (IL-2) has antitumor activity in some patients with metastatic melanoma. We have analyzed molecular mechanisms of TIL recognition of human melanoma. Some cultured TILs specifically lysed autologous and some allogeneic melanomas sharing a variety of class I major histocompatibility complex (MHC) molecules. HLA-A2-restricted melanoma-specific TILs lysed many HLA-A2+ melanoma cell lines from different patients but failed to lyse HLA-A2- melanoma and HLA-A2+ nonmelanoma cell lines. However, these TILs were capable of lysing many naturally HLA-A2- melanomas after introduction of the HLA-A2.1 gene by vaccinia virus. These results indicate that shared melanoma antigens (Ag) are expressed in melanomas regardless of their human leukocyte antigen types. In order to identify these shared melanoma Ags, we have tested some known proteins expressed in melanoma. Expression of tyrosinase or HMB45 Ag correlated with lysis of TILs. We are also attempting to isolate antigenic peptides by high performance liquid chromatography separation and genes encoding melanoma Ag by cDNA expression cloning. The T-cell component of the antimelanoma response was also analyzed by determining the genetic structure of the T-cell receptor (TCR) used by melanoma TILs. However, we did not observe common TCR variable region usage by different melanoma TILs. We could establish melanoma cell clones and lines resistant to TIL lysis due to the absence of or defects in the expression of Ag, MHC, or beta 2-microglobulin molecules. These data indicate multiple mechanisms for melanoma escape from T-cell immunosurveillance.(ABSTRACT TRUNCATED AT 250 WORDS)

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FIG. 1

FIG. 1

T-cell recognition of melanoma antigenic peptides in the context of different class I MHCs. Common (Pr1) or different (Pr2, 3) melanoma Ag proteins may provide Ag peptides (Ag1, Ag2) to different MHCs, and these Ag peptides may be recognized by T-cells in the context of different MHCs. If such common Ag proteins exist, we may be able to use them to immunize patients expressing a variety of HLA types.

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