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Cancer Immunology, Immunotherapy

, Volume 47, Issue 4, pp 191–197 | Cite as

Spontaneous T cell responses to melanoma differentiation antigens from melanoma patients and healthy subjects

  • Qiyuan Chen
  • Heather Jackson
  • Peter Gibbs
  • Ian D. Davis
  • Joseph Trapani
  • Jonathan Cebon
ORIGINAL ARTICLE

Abstract

The spontaneous cytotoxic T cell responses to melanoma differentiation antigens and influenza matrix peptide were compared in 20 HLA-A2+ melanoma patients and 17 healthy A2+ individuals. Cytotoxic T lymphocyte (CTL) responses were determined by mixed lymphocyte peptide culture (MLPC) involving two stimulations of unfractionated peripheral blood lymphocytes (PBLs) with peptide in vitro. CTL responses to Melan-A 9-mer (amino acids 27–35, AAGIGILTV) peptide were detected in 4 out of 16 normal individuals, but in none of the melanoma patients. CTL specific for influenza matrix peptide were frequently found in both normal individuals and melanoma patients, suggesting that generalized immuno-suppression was not responsible for this difference. No significant responses were observed in either normal individuals or melanoma patients to Melan-A 10-mer (26–35, EAAGIGILTV), two gp100 epitopes (280–288, YLEPGPVTA; 457–466, LLDGTATLRL) and two tyrosinase epitopes (1–9, MLLAVLYCL; 368–376, YMDGMSQV). Melan-A (27–35)-specific CTL cells generated by normal individuals and melanoma patients recognized both synthetic peptide-pulsed T2 cells and two HLA-A2+, Melan-A+ melanoma cell lines (ME272, LAR1) in an antigen-specific, MHC class I restricted manner. T cells generated against Melan-A 9-mer were also able to recognize Melan-A 10-mer-pulsed target cells. Spontaneous CTL responses to Melan-A 9-mer from three known responder normal individuals were further evaluated over a prolonged time course (6–11 months). All 3 subjects demonstrated specific Melan-A 9-mer responses throughout the study period, although lytic activity fluctuated over time for a given individual. We found the MLPC assay to be reliable and easy to perform for monitoring T cell responses, although it may still not be sufficiently sensitive to detect low numbers of precursor T cells.

Key words Melanoma Differentiation antigens Melan-A Cytotoxic lymphocytes 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Qiyuan Chen
    • 1
  • Heather Jackson
    • 1
  • Peter Gibbs
    • 1
  • Ian D. Davis
    • 1
  • Joseph Trapani
    • 2
  • Jonathan Cebon
    • 3
  1. 1.Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Austin Repat Cancer Centre, Heidelberg, VIC 3084, AustraliaAU
  2. 2.Cellular Cytotoxicity Laboratory, Austin Research Institute, Austin Hospital, Heidelberg, VIC 3084, AustraliaAU
  3. 3.Ludwig Institute for Cancer Research, Oncology, Austin Hospital, Heidelberg, VIC 3084, Australia e-mail: Jonathan.Cebon@Ludwig.edu.au Tel.: +6-3-94576933,Fax: +6-3-94576698AU

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