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Published on: August 31, 2014
Influence of HLA-C expression level on HIV control
Richard Apps1, Ying Qi, Jonathan M Carlson
1Cancer and Inflammation Program, Laboratory of Experimental Immunology, Science Applications International Corporation-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Higher human leukocyte antigen C (HLA-C) expression improves HIV control by enhancing immune responses. This effect is independent of specific HLA-C types and observed across diverse populations, suggesting a broad role in disease.
Area of Science:
- Immunogenetics
- Human Virology
- Complex Disease Etiology
Background:
- A specific variant near human leukocyte antigen C (HLA-C) significantly impacts HIV control in European Americans, correlating with HLA-C expression levels.
- HLA-C plays a crucial role in immune responses, particularly in cytotoxic T lymphocyte (CTL) activity, which is vital for controlling viral infections like HIV.
Purpose of the Study:
- To characterize cell surface expression levels of all common HLA-C allotypes.
- To directly assess the impact of varying HLA-C expression levels on HIV infection outcomes in a large, diverse cohort.
- To investigate the relationship between HLA-C expression, CTL responses, and viral evolution in HIV.
Main Methods:
- Genome-wide association study (GWAS) analysis to identify genetic variants associated with HIV control.
- Flow cytometry or similar techniques to quantify cell surface expression of HLA-C allotypes.
- Statistical analysis of 5243 individuals to correlate HLA-C expression levels with HIV disease progression and immune responses.
Main Results:
- Increased HLA-C expression demonstrated a protective effect against multiple HIV outcomes in both African and European Americans.
- This protective effect was independent of specific HLA-C alleles and their linkage disequilibrium with HLA-B and HLA-A.
- Higher HLA-C expression correlated with enhanced cytotoxic T lymphocyte (CTL) responses and a higher frequency of viral escape mutations.
- Conversely, elevated HLA-C expression was linked to adverse outcomes in Crohn's disease.
Conclusions:
- HLA-C expression level, rather than just allelic type, is a critical factor in modulating HIV disease progression.
- The findings suggest a broader role for HLA expression levels in influencing the pathogenesis of various human diseases, including autoimmune conditions.
- Targeting or understanding HLA-C expression could offer new therapeutic strategies for HIV and potentially other immune-mediated diseases.
