International Immunology, Vol 9, 327-338, Copyright © 1997 by Oxford University Press
TJ Tsomides, EB Reilly and HN Eisen
A line of tumor-infiltrating lymphocytes (660TIL) specifically lysed the
autologous HLA-A2+ melanoma (660MEL) and also most A2+ melanoma cell lines.
We immunoprecipitated A2 from a large number (>10(12)) of 660MEL cells,
extracted naturally processed peptides, fractionated them by HPLC, screened
the fractions for recognition by 660TIL, and found a single predominant and
a minor peak of activity. Although too little was recovered of the major
660MEL peptide to establish its sequence, HPLC fingerprinting showed that
it did not correspond to any of the known A2-associated melanoma peptides
recognized by T cells, including peptides from tyrosinase, MART-1/Melan-A,
gp100 and MAGE-3. The major 660MEL antigenic peptide appears to be derived
from MART-1/Melan-A but is neither AAGIGILTV nor ILTVILGVL nor any other
MART-1/Melan-A peptide containing the A2 consensus motif. The multiplicity
of melanoma peptides recognized by CD8+ T cells, most of which are
non-mutated (including most likely the present 660MEL peptide), suggests
the existence of unknown mechanisms, perhaps similar to those operating in
autoimmune disorders, whereby T cells that recognize normal 'self'
sequences become activated.
ARTICLES
Anti-melanoma cytotoxic T lymphocytes (CTL) recognize numerous antigenic peptides having 'self' sequences: autoimmune nature of the anti-melanoma CTL response
Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
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