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MHC class II-mediated antigen presentation by melanoma cells
M S Brady1, D D Eckels, S Y Ree
1Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Journal of Immunotherapy with Emphasis on Tumor Immunology : Official Journal of the Society for Biological Therapy
|November 1, 1996
Summary
Melanoma cells can process and present antigens via major histocompatibility complex (MHC) class II molecules, stimulating T-cell responses. This suggests a functional role for MHC class II in melanoma progression and potential therapeutic targeting.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Major histocompatibility complex (MHC) class II expression is typically limited to antigen-presenting cells (APCs).
- Melanoma frequently exhibits constitutive MHC class II expression, linked to tumor progression.
Purpose of the Study:
- To investigate the functional capacity of MHC class II molecules in melanoma cells.
- To determine if melanoma cells can process and present antigens to CD4+ T cells.
Main Methods:
- Melanoma cell lines were tested for their ability to process antigens and present peptides via MHC class II.
- T-cell proliferation assays were performed using peptide-specific CD4+ T-cell clones.
- Blocking studies with CTLA-4Ig and CD54 (ICAM-1) were conducted to assess costimulatory molecule roles.
Main Results:
- Melanoma cells efficiently processed antigens and presented peptides via MHC class II, inducing significant T-cell proliferation (5-26 fold increase).
- CD28 costimulation was not required for this T-cell response.
- Blocking CD54 (ICAM-1) reduced T-cell proliferation in response to melanoma APCs, but not B cells.
Conclusions:
- MHC class II molecules on melanoma cells are functional, indicating intact antigen-processing pathways.
- Melanoma cells can effectively present antigens to CD4+ T cells, potentially contributing to tumor progression.
- CD54 (ICAM-1) plays a significant role in peptide presentation by melanoma cells.