Previous studies have shown that recognition of
melanoma by cytotoxic T lymphocytes may be restricted by
HLA-A1, A2 and other
HLA antigens. The present study examined the cytotoxic specificity and major histocompatibility complex restriction of cloned cytotoxic T lymphocytes (CTL) isolated from a patient with the HLA phenotype A3,31 who had been immunized with a
vaccine prepared from HLA-A1,3
melanoma cells. Cytotoxic assays against HLA-typed allogeneic
melanoma cells indicated that cloned CTL from the patient were able to kill allogeneic
melanoma cells expressing
HLA-A1 but not other HLA-A1-positive cells. Studies on a representative clone indicated that proliferation and
cytokine (tumour
necrosis factor alpha) production in response to
melanoma cells was also associated with
HLA-A1 on
melanoma cells. Response to the
melanoma cells was associated with
interleukin-4 (IL-4) rather than
IL-2 production. The
antigen recognized in the context of
HLA-A1 on allogeneic
melanoma cells was detected in cytotoxic assays on cells from 9 of 12 HLA-A1+
melanoma cell lines and did not appear to be the product of the MAGE-1 or -3 genes. These findings suggest that T cells can recognize
melanoma antigens in the context of
alloantigens and that allogeneic
vaccines containing "immunodominant"
alloantigens may generate CTL that are ineffective against autologous
melanoma. The study does not, however, exclude the possibility that CTL with specificity to the latter may be activated by allogeneic
vaccines, and further studies are needed to answer this question.