ERAP1 and ERAP2 Haplotypes Influence Suboptimal HLA-B*27:05-Restricted Anti-Viral CD8+ T Cell Responses...

Area of Science:

• Immunogenetics
• Rheumatology
• Molecular Biology

Background:

• The human leukocyte antigen (HLA)-B*27 allele is strongly linked to ankylosing spondylitis (AS).
• Endoplasmic Reticulum AminoPeptidases (ERAPs) 1 and 2 are critical for shaping HLA class I epitopes and are AS susceptibility factors.
• Previous research identified a B*27:05-restricted CD8+ T cell response to an Epstein-Barr virus (EBV) peptide (pEBNA3A) lacking a classic B*27 binding motif.

Purpose of the Study:

• To investigate the role of ERAP1/2 haplotypes in modulating CD8+ T cell responses to suboptimal peptides presented by HLA-B*27.
• To explore the presentation of viral and self-peptides with suboptimal N-terminal motifs by the HLA-B*27:05 allele.

Main Methods:

• Analysis of ERAP1/2 haplotype correlations with CD8+ T cell responses in HLA-B*27:05 subjects.
• Assessment of HLA-B*27:05 allele's capacity to present peptides with suboptimal N-terminal motifs, including viral and self-peptides.

Main Results:

• A specific ERAP1/2 haplotype was found to negatively correlate with the previously identified B*27:05-restricted CD8+ T cell response to pEBNA3A.
• The HLA-B*27:05 allele demonstrated the ability to present peptides, such as the self-peptide pDYNEIN, that share the suboptimal N-terminal 'RP' motif.

Conclusions:

• The study highlights a cooperative interaction between HLA-B*27 and ERAP1/2 variants in determining CD8+ T cell reactivity to suboptimal viral and self-peptides.
• Findings suggest that the composition of the B*27:05 peptidome, influenced by ERAP1/2 activity, may be crucial in AS pathogenesis and warrants further investigation.