HLA alleles, disease severity, and age associate with T-cell responses following infection with SARS-CoV-2

Bjarnadóttir, Kristbjörg; Norddahl, Gudmundur L.; Halldorsson, Gisli H.; Melsted, Páll; Gunnarsdóttir, Kristbjörg; Ívarsdóttir, Erna V.; Ólafsdóttir, Þórhildur; Arnthórsson, Asgeir Ö.; Theódórs, Fannar; Eyþórsson, Elías; Helgason, Daði; Másson, Gísli; Bjarnadottir, Sólveig; Saevarsdóttir, Saedís; Runólfsdóttir, Hrafnhildur Linnet; Ólafsson, Ísleifur; Saemundsdottir, Jona; Sigurðsson, Martin I; Ingvarsson, Ragnar Freyr; Pálsson, Runólfur; Þorgeirsson, Guðmundur; Halldórsson, Bjarni V.; Hólm, Hilma; Kristjánsson, Már; Sulem, Patrick; Þorsteinsdóttir, Unnur; Jónsdóttir, Ingileif; Guðbjartsson, Daníel F.; Stefánsson, Kāri

doi:10.1038/s42003-022-03893-w

Cited by 6 publications

(3 citation statements)

References 49 publications

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“…This result implies that an observed TCRβ shared among multiple subjects in a given HLA context is very likely paired with one or a very small set of compatible TCRαs. In this respect, TCRβ repertoires are not unique; analysis of TCRα repertoires would lead to similar results and conclusions as presented here 8 . Thus, our ability to identify HLA specific TCRs using only a single chain of the TCR heterodimer is not a characteristic of the TCRβs but rather a consequence of T cell immunology and our procedure for identifying enhanced sequences.…”

Section: Discussionsupporting

confidence: 80%

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Large-scale statistical mapping of T-cell receptorβsequences to Human Leukocyte Antigens

Zahid,

Taniguchi,

Ebert

et al. 2024

Preprint

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Interactions between diverse sets of T-cell receptors (TCRs) and peptides presented by human leukocyte antigens (HLAs) are the foundation of the adaptive immune system but population-level analysis of TCR-HLA interactions is lacking. Here we use the TCRβ repertoire of 4,144 HLA-genotyped subjects to associate ∼10^6 public TCRs (i.e., TCRs observed in multiple subjects) with specific HLAs, providing a new window into the functional characteristics of HLAs. We find that the vast majority of these HLA-associated public TCRs are specific to unique HLA allotypes, not allelic groups, and to the paired α-β heterodimer of class II HLAs though we observe some exceptions and also that the breadth of the TCR response is proportional to HLA zygosity. Identification of public HLA-specific TCRs permits highly accurate imputation of 248 class I and II HLAs from the TCRβ repertoire alone. Notably, 45 HLA-DP and -DQ heterodimers cannot be imputed due to a lack of associated TCRs, despite high representation in our training set. Gene linkage analysis indicates these heterodimers primarily arise from trans-complementation resulting in non-functional α-β pairs. Cell sorting, clonal expansion, and comparisons between SARS-CoV-2-exposed and -naive populations suggest that public class I and class II HLA-associated TCRs we identify are primarily expressed on CD8+ and CD4+ memory T cells, respectively, which are responding to a mix of common antigens. Our results recapitulate fundamental immunology, provide critical new insights into the functionality of HLAs, and demonstrate the power and potential of population-level TCR repertoire sequencing.

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Section: Discussionsupporting

confidence: 80%

“…TCRs on the surface of T cells interact with the peptides presented by HLAs (pHLA). The TCR-pHLA interaction is a key mechanism of adaptive immunity and plays a central role in the immune system's response to infections, cancers, allergens and self-tissues targeted in autoimmunity and transplantation (3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Large-scale statistical mapping of T-cell receptorβsequences to Human Leukocyte Antigens

Zahid,

Taniguchi,

Ebert

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Researchers in Iceland analyzed SARS-CoV-2 reactive T-cell responses in 768 convalescent SARS-CoV-2-infected (cases) and 500 uninfected (controls) Icelanders. The strongest association was between increasing IFN-γ secreting N-reactive CD8 + T-cell responses and HLA-B*07:02, followed by HLA-C*07:02 [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

HLA Genotypes in Patients with Infection Caused by Different Strains of SARS-CoV-2

Бубнова

Pavlovа

Terentieva

et al. 2022

IJERPH

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The aggressive infectious nature of SARS-CoV-2, its rapid spread, and the emergence of mutations necessitate investigation of factors contributing to differences in SARS-CoV-2 susceptibility and severity. The role of genetic variations in the human HLA continues to be studied in various populations in terms of both its effect on morbidity and clinical manifestation of illness. The study included 484 COVID-19 convalescents (northwest Russia residents of St. Petersburg). Cases in which the responsible strain was determined were divided in two subgroups: group 1 (n = 231) had illness caused by genovariants unrelated to variant of concern (VOC) strains; and group 2 (n = 80) had illness caused by the delta (B.1.617.2) VOC; and a control group (n = 1456). DNA typing (HLA-A, B, DRB1) was performed at the basic resolution level. HLA-A*02 was associated with protection against infection caused by non-VOC SARS-CoV-2 genetic variants only but not against infection caused by delta strains. HLA-A*03 was associated with protection against infection caused by delta strains; and allele groups associated with infection by delta strains were HLA-A*30, B*49, and B*57. Thus, in northwest Russia, HLA-A*02 was associated with protection against infection caused by non-VOC SARS-CoV-2 genetic variants but not against delta viral strains. HLA-A*03 was associated with a reduced risk of infection by delta SARS-CoV-2 strains. HLA-A*30, HLA-B*49, and HLA-B*57 allele groups were predisposing factors for infection by delta (B.1.617.2) strains.

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Spotlight on contributory role of host immunogenetic profiling in SARS-CoV-2 infection: Susceptibility, severity, mortality, and vaccine effectiveness

Yazdanparast,

Bakhtiyaridovvombaygi,

Mikanik

et al. 2023

Life Sciences

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HLA alleles, disease severity, and age associate with T-cell responses following infection with SARS-CoV-2

Cited by 6 publications

References 49 publications

Large-scale statistical mapping of T-cell receptorβsequences to Human Leukocyte Antigens

Large-scale statistical mapping of T-cell receptorβsequences to Human Leukocyte Antigens

HLA Genotypes in Patients with Infection Caused by Different Strains of SARS-CoV-2

Spotlight on contributory role of host immunogenetic profiling in SARS-CoV-2 infection: Susceptibility, severity, mortality, and vaccine effectiveness

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