Residues in HLA class I that Account for Variation of the HIV Host Response Distinctly Modulate Interactions with TCR and KIRs Article Swipe
Rhoda Tano-Menka
,
Nishant K. Singh
,
Itai Muzhingi
,
Xiaolong Li
,
Michael V Mandanas
,
Clarety Kaseke
,
Angela Zhang
,
Funsho Ogunshola
,
Liza Vecchiarello
,
Alicja Piechocka‐Trocha
,
Arman Bashirova
,
Michael E. Birnbaum
,
Mary Carrington
,
Bruce D. Walker
,
Gaurav D. Gaiha
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-2105002/v1
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-2105002/v1
Polymorphisms in human leukocyte antigen ( HLA ) genes strongly influence outcomes to HIV infection. However, the underlying mechanisms by which certain alleles mediate protection is not well understood. Here we systematically investigate residues within HLA class I molecules (at positions 67, 70, 97 and 156) that have been demonstrated by genetic studies to explain the observed variation of HLA class I alleles on HIV infection. Through a detailed assessment of the protective HLA-B*5701 allele, we find that each of these residues has distinct effects on either HIV-specific CD8+ T cell recognition (67, 70, 156), stabilization of HLA class I-peptide complexes (67, 156), binding of HLA class I-peptide to HIV-specific T cell receptors (70, 156) or KIR3DL1 (97). Structural analyses illustrate that residue mutations uniquely affect the residue microenvironment of the class I binding groove to impact interactions between HLA-peptide complexes with TCR and KIR. These results thereby provide a structural and mechanistic basis for the HLA association with HIV disease outcome. Moreover, they definitively demonstrate that the major host genetic determinant of HIV control is modulation of the stability and conformation of viral peptides by HLA class I for recognition by both the innate and adaptive immune system.
Related Topics
Concepts
Human leukocyte antigen
T-cell receptor
Biology
Allele
Immunology
HLA-B Antigens
CD8
Genetics
Receptor
Peptide
Major histocompatibility complex
Immune system
T cell
Gene
Antigen
Biochemistry
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-2105002/v1
- https://www.researchsquare.com/article/rs-2105002/latest.pdf
- OA Status
- green
- Cited By
- 2
- References
- 40
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4297337877
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4297337877Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-2105002/v1Digital Object Identifier
- Title
-
Residues in HLA class I that Account for Variation of the HIV Host Response Distinctly Modulate Interactions with TCR and KIRsWork title
- Type
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preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-09-27Full publication date if available
- Authors
-
Rhoda Tano-Menka, Nishant K. Singh, Itai Muzhingi, Xiaolong Li, Michael V Mandanas, Clarety Kaseke, Angela Zhang, Funsho Ogunshola, Liza Vecchiarello, Alicja Piechocka‐Trocha, Arman Bashirova, Michael E. Birnbaum, Mary Carrington, Bruce D. Walker, Gaurav D. GaihaList of authors in order
- Landing page
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https://doi.org/10.21203/rs.3.rs-2105002/v1Publisher landing page
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https://www.researchsquare.com/article/rs-2105002/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.researchsquare.com/article/rs-2105002/latest.pdfDirect OA link when available
- Concepts
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Human leukocyte antigen, T-cell receptor, Biology, Allele, Immunology, HLA-B Antigens, CD8, Genetics, Receptor, Peptide, Major histocompatibility complex, Immune system, T cell, Gene, Antigen, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
- Citations by year (recent)
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2023: 2Per-year citation counts (last 5 years)
- References (count)
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40Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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