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Positional scanning-synthetic peptide library-based analysis of self- and pathogen-derived peptide cross-reactivity with tumor-reactive Melan-A-specific CTL.

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  • 2002-11-08
Published in:
  • Journal of immunology (Baltimore, Md. : 1950). - 2002
Antigens, Bacterial
Antigens, Neoplasm
Antigens, Viral
Autoantigens
Clone Cells
Combinatorial Chemistry Techniques
Cytotoxicity Tests, Immunologic
Cytotoxicity, Immunologic
Epitopes, T-Lymphocyte
HLA-A2 Antigen
Humans
MART-1 Antigen
Melanoma
Neoplasm Proteins
Peptide Fragments
Peptide Library
Protein Binding
T-Lymphocytes, Cytotoxic
Tumor Cells, Cultured
English Synthetic combinatorial peptide libraries in positional scanning format (PS-SCL) have recently emerged as a useful tool for the analysis of T cell recognition. This includes identification of potentially cross-reactive sequences of self or pathogen origin that could be relevant for the understanding of TCR repertoire selection and maintenance, as well as of the cross-reactive potential of Ag-specific immune responses. In this study, we have analyzed the recognition of sequences retrieved by using a biometric analysis of the data generated by screening a PS-SCL with a tumor-reactive CTL clone specific for an immunodominant peptide from the melanocyte differentiation and tumor-associated Ag Melan-A. We found that 39% of the retrieved peptides were recognized by the CTL clone used for PS-SCL screening. The proportion of peptides recognized was higher among those with both high predicted affinity for the HLA-A2 molecule and high predicted stimulatory score. Interestingly, up to 94% of the retrieved peptides were cross-recognized by other Melan-A-specific CTL. Cross-recognition was at least partially focused, as some peptides were cross-recognized by the majority of CTL. Importantly, stimulation of PBMC from melanoma patients with the most frequently recognized peptides elicited the expansion of heterogeneous CD8(+) T cell populations, one fraction of which cross-recognized Melan-A. Together, these results underline the high predictive value of PS-SCL for the identification of sequences cross-recognized by Ag-specific T cells.
Language
  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/93606
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