Shared HLA Class I and II Alleles and Clonally Restricted Public and Private Brain-Infiltrating αβ T Cells in a Cohort of Rasmussen Encephalitis Surgery Patients

Dandekar, Sugandha; Wijesuriya, Hemani; Geiger, Tim; Hamm, David; Mathern, Gary W.; Owens, Geoffrey C.

doi:10.3389/fimmu.2016.00608

Cited by 11 publications

(9 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sequencing. TCR immunosequencing was done according to the immunoSEQ assay (Adaptive Biotechnologies) as previously described (38,61,65); for details please see SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Sex bias in MHC I-associated shaping of the adaptive immune system

Schneider‐Hohendorf

Görlich²,

Savola

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

HLA associations, T cell receptor (TCR) repertoire bias, and sex bias have independently been shown for many diseases. While some immunological differences between the sexes have been described, they do not fully explain bias in men toward many infections/cancers, and toward women in autoimmunity. Next-generation TCR variable beta chain (TCRBV) immunosequencing of 824 individuals was evaluated in a multiparametric analysis including HLA-A -B/MHC class I background, TCRBV usage, sex, age, ethnicity, and TCRBV selection/expansion dynamics. We found that HLA-associated shaping of TCRBV usage differed between the sexes. Furthermore, certain TCRBVs were selected and expanded in unison. Correlations between these TCRBV relationships and biochemical similarities in HLA-binding positions were different in CD8 T cells of patients with autoimmune diseases (multiple sclerosis and rheumatoid arthritis) compared with healthy controls. Within patients, men showed higher TCRBV relationship Spearman's rhos in relation to HLA-binding position similarities compared with women. In line with this, CD8 T cells of men with autoimmune diseases also showed higher degrees of TCRBV perturbation compared with women. Concerted selection and expansion of CD8 T cells in patients with autoimmune diseases, but especially in men, appears to be less dependent on high HLA-binding similarity than in CD4 T cells. These findings are consistent with studies attributing autoimmunity to processes of epitope spreading and expansion of low-avidity T cell clones and may have further implications for the interpretation of pathogenic mechanisms of infectious and autoimmune diseases with known HLA associations. Reanalysis of some HLA association studies, separating the data by sex, could be informative.

show abstract

“…Sequencing. TCR immunosequencing was done according to the immunoSEQ assay (Adaptive Biotechnologies) as previously described (38,61,65); for details please see SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Sex bias in MHC I-associated shaping of the adaptive immune system

Schneider‐Hohendorf

Görlich²,

Savola

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…We previously found that some of the most abundant Vb clonotypes in brain tissue from 14 RE patients were public (31).…”

Section: Discussionmentioning

confidence: 97%

Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures

et al. 2021

Self Cite

View full text Add to dashboard Cite

Using a targeted transcriptomics approach, we have analyzed resected brain tissue from a cohort of 53 pediatric epilepsy surgery cases, and have found that there is a spectrum of involvement of both the innate and adaptive immune systems as evidenced by the differential expression of immune-specific genes in the affected brain tissue. The specimens with the highest expression of immune-specific genes were from two Rasmussen encephalitis cases, which is known to be a neuro-immunological disease, but also from tuberous sclerosis complex (TSC), focal cortical dysplasia, and hemimegalencephaly surgery cases. We obtained T cell receptor (TCR) Vβ chain sequence data from brain tissue and blood from patients with the highest levels of T cell transcripts. The clonality indices and the frequency of the top 50 Vβ clonotypes indicated that T cells in the brain were clonally restricted. The top 50 Vβ clonotypes comprised both public and private (patient specific) clonotypes, and the TCR Vβ chain third complementarity region (CDR3) of the most abundant public Vβ clonotype in each brain sample was strikingly similar to a CDR3 that recognizes an immunodominant epitope in either human cytomegalovirus or Epstein Barr virus, or influenza virus A. We found that the frequency of 14 of the top 50 brain Vβ clonotypes from a TSC surgery case had significantly increased in brain tissue removed to control recurrent seizures 11 months after the first surgery. Conversely, we found that the frequency in the blood of 18 of the top 50 brain clonotypes from a second TSC patient, who was seizure free, had significantly decreased 5 months after surgery indicating that T cell clones found in the brain had contracted in the periphery after removal of the brain area associated with seizure activity and inflammation. However, the frequency of a public and a private clonotype significantly increased in the brain after seizures recurred and the patient underwent a second surgery. Combined single cell gene expression and TCR sequencing of brain-infiltrating leukocytes from the second surgery showed that the two clones were CD8 effector T cells, indicating that they are likely to be pathologically relevant.

show abstract

“…Within the DQ molecule, 76 polymorphisms have been identified on DQA and 978 have been found on DQB, which allows for a wide range of peptide-binding specificities. Nevertheless, gene mutations causing malfunction of DQA1 and DQB1 were found to be associated with autoimmune disorders such as rheumatoid arthritis [29,30], multiple sclerosis [31,32], and even cancer [33]. In addition, DQA1 and DQB1 gene mutations have also been found to be associated with adverse drug reactions and drug efficacy.…”

Section: Discussionmentioning

confidence: 99%

HLA-DQA1 and DQB1 Alleles are Associated with Acitretin Response in Patients with Psoriasis

Zhou¹,

He²,

Kuang³

et al. 2022

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

Background: Psoriasis vulgaris is an immune-mediated inflammatory skin disease. Although the pathogenesis of psoriasis is unclear, genetic susceptibility, such as HLA-C*06:02, is believed to be a major risk factor. However, there is a paucity of knowledge regarding the relationship between genetics and the response to systemic treatment of psoriasis. We hypothesized that genetic variations in human leukocyte antigen (HLA) genes may act as predictors of acitretin treatment in psoriasis. The aim of our study was to explore the presence of HLA gene variants in patients with moderate-to-severe psoriasis receiving acitretin treatment. Methods: A total of 100 Han Chinese patients with psoriasis completed the study. 24 patients including 16 responders and 8 non-responders underwent deep sequencing by MHC targeted region capture and 76 samples were genotyped by Sanger sequencing (SBT) based HLA typing for validation. Results: Regressions with adjustment for age, sex, body mass index (BMI), and baseline psoriasis area and severity index (PASI) revealed that two HLA alleles (HLA-DQA1*:02:01, DQB*:02:02) were associated with the response to acitretin. The DQA1*0201-positive patients showed a better response to acitretin compared to the DQA1*0201-negative patients (relative risk (RR) = 10.34, 95% confidence interval (CI): 2.62-40.77, p = 0.001), and the DQB1*0202-positive patients manifested a better response to acitretin when compared to the DQB1*0202-negative patients (RR = 21.01, 95% CI: 2.53-174.27, p = 0.005). Conclusions: Our observations support the potential role of HLA-DQA1*:02:01 and DQB*:02:02 as pharmacogenetic markers of the acitretin response in patients with psoriasis.

show abstract

Shared HLA Class I and II Alleles and Clonally Restricted Public and Private Brain-Infiltrating αβ T Cells in a Cohort of Rasmussen Encephalitis Surgery Patients

Cited by 11 publications

References 62 publications

Sex bias in MHC I-associated shaping of the adaptive immune system

Sex bias in MHC I-associated shaping of the adaptive immune system

Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures

HLA-DQA1 and DQB1 Alleles are Associated with Acitretin Response in Patients with Psoriasis

Contact Info

Product

Resources

About