A superagonist variant of peptide MART1/Melan A27-35 elicits anti-melanoma CD8+ T cells with enhanced functional characteristics: implication for more effective immunotherapy

Cancer Res. 1999 Jan 15;59(2):301-6.


In the present study, we show that a singly substituted peptide derived from the epitope MART1(27-35) and containing a Leu in position 1 (LAGIGILTV; 1L) behaves as a superagonist by in vitro inducing specific T cells with enhanced immunological functions. 1L-specific CTLs can be raised from peripheral blood of HLA-A2+ melanoma patients more efficiently than T cells specific for the cognate peptide. These T cells show a greater sensitivity to native MART1(27-35) when compared with CTL variable raised to parental peptide from the same patients. More importantly, anti-1L but not anti-native T cells display high levels of interferon gamma production at early time points, and readily secreted interleukin-2 in response to native epitope endogenously presented by melanoma cells. Additionally, anti-1L T cells are insensitive to the inhibitory effects of MART1(27-35) natural analogues that antagonize the lytic response of CTLs raised to the cognate peptide. Analysis of T-cell receptor variable beta usage suggests that the native and 1L peptides stimulate different components of the MART1(27-35)-reactive T cell population. These data provide rationale to the use of superagonist analogues of tumor antigens for inducing in vivo immunization potentially able to overcome tumor immune escape and mediate a more significant control of tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes / immunology*
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunization
  • Immunotherapy
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Melanoma / immunology*
  • Melanoma / therapy
  • Neoplasm Proteins / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics


  • Epitopes
  • HLA-A2 Antigen
  • Interleukin-2
  • MART-1-Melan-A(27-35) epitope
  • Neoplasm Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Interferon-gamma