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Definition of HLA-Dw and HLA-DPw Determinants by the Primed Lymphocyte Test
Published in M. Kam, Jeffrey L. Bidwell, Handbook of HLA TYPING TECHNIQUES, 2020
When the PLT test was first described it was seen as an ideal substitute for the typing of HLA-Dw specificities by homozygous typing cells (HTCs) since Dw typing could be performed in 2 d rather that in 6 or 7 d and the HLA-Dw specificity could be defined by a positive response rather than a lack of response, which is the criterion used for the Dw definition by HTC typing. But more importantly, it provided the possibility for defining some HLA-Dw determinants for which HTCs were not available.7,8 However, in spite of all these advantages, it was soon realized that the PLT test was less discriminatory than HTC typing due to the fact that in the primary MLC test, the HLA-Dw (i.e., DRB1 gene products) are the main stimulatory determinants, whereas in the PLT test other HLA class II products such as HLA-DQ and -DP are also able to induce secondary stimulation.9,10 In fact the PLT test has been used primarily for the definition of the HLA-DP antigens.
Immunopathogenesis of Type I Diabetes Mellitus
Published in George S. Eisenbarth, Immunotherapy of Diabetes and Selected Autoimmune Diseases, 2019
Richard J. Keller, George S. Eisenbarth
For TH cells to be activated, they need to see antigen in association with class II (HLA, DP, Q, R) molecules. Class II molecules are normally present on B lymphocytes, antigen presenting cells (e. g., macrophages), dendritic cells, activated T lymphocytes, some capillary endothelial cells, and many epithelial cells, inducing pancreatic ducts.144
Peanut Allergy Biomolecular Characterization for Development of a Peanut T-Cell Epitope Peptide Therapy
Published in Andreas L. Lopata, Food Allergy, 2017
Jennifer M. Rolland, Sara R. Prickett, Robyn E. O’Hehir
There is no known HLA-association with peanut allergy. An important consideration when selecting peptides for immunotherapy is whether they can be presented by different HLA class II molecules and therefore be suitable for treating a genetically diverse human population. Consistent with T-cell epitopes of other major allergens, the dominant T-cell epitopes of Ara h 1 and 2 demonstrate strong and degenerate HLA-binding (Prickett et al. 2011, 2013). The HLA-restriction of T-cell recognition of each epitope was assessed in different donors using HLA blocking antibodies and HLA-genotyping and showed that each epitope could be presented on two or more different HLA-molecules. The epitopes were collectively presented on a combination of HLA-DR, HLA-DQ and HLA-DP molecules. Inclusion of HLA-DQ and/or HLA-DP restricted T-cell epitopes is particularly advantageous for a T-cell targeted therapeutic since these HLA-molecules tend to be more conserved in mixed populations than HLA-DR molecules, enabling broader population coverage with fewer T-cell epitope sequences. DeLong et al. (2011) used a tetramer guided epitope mapping approach to identify a panel of Ara h 1 T-cell epitopes and similarly demonstrated presentation of the HLA-DR-restricted epitopes by multiple HLA- DR molecules.
Evaluation of HLA class I and HLA class II allele profile and its relationship with clinical features in patients with alopecia areata: a case–control study
Published in Journal of Dermatological Treatment, 2022
Yıldız Hayran, Melek Gunindi Korkut, Ayşe Öktem, Orhan Şen, Güneş Gür Aksoy, Füsun Özmen
The exact mechanism of HLA autoimmune or inflammatory disease association is not fully understood but many theories have been proposed. One of the most accepted theory is the aberrant selection of self-reactive T cells and the immune response against self-antigens due to cross-reactivity between foreign and self-epitopes (49–51). HLA class I molecules (HLA-A, HLA-B, and HLA-C) present antigens to CD8+ T lymphocytes and HLA class II molecules (HLA-DQ, HLA-DR, and HLA-DP) to CD4+ T cell initiating CD4+ and CD8+ T lymphocyte mediated immune responses. The role of CD4+ and CD8+ T lymphocytes in pathogenesis of AA has been investigated in many studies supporting the evidence of both HLA class I and HLA class II association with increased AA risk. CD8+ cytotoxic T cells and CD4+ helper T cells are the major inflammatory cells infiltrating hair follicles of patients with AA (52). The animal models support the pivotal role of T cells through developing AA in C3H/Hej mice by transferring T cells or vice versa showing the hair regrowth in DEBR model by reducing CD4+ and CD8+ T cells (53,54). HLA-B*13 and HLA-DRB1*11 molecules may present different antigens to different T cell initiating both CD8+ and CD4+ T cell mediated immune responses. Similar to their involvement in pathogenesis of AA, both CD8+ and CD4+ T lymphocyte-mediated immune responses may be also associated with prognosis. Larger studies investigating HLA − treatment response are needed.
Targeting KRAS mutations with HLA class II-restricted TCRs for the treatment of solid tumors
Published in OncoImmunology, 2021
Pierre Dillard, Nicholas Casey, Sylvie Pollmann, Patrik Vernhoff, Gustav Gaudernack, Gunnar Kvalheim, Sébastien Wälchli, Else Marit Inderberg
Vaccine-specific T cell responses in patient samples in the clinical study CTN Ras 98010 were tested as previously described in 3H-thymidine incorporation assays.21 The Stimulation Index (SI) was defined as proliferation with peptide divided by proliferation without peptide. SI ≥ 2 was considered a positive response and counts per minute (cpm) of all tested conditions were used and plotted. Between February and April 2006, blood samples from 5‐year survivors were collected and analyzed for long‐term immunological response using the same assay. T cells were cloned by limiting dilution as previously described, then expanded using irradiated PBMCs as feeder cells, PHA (Oxoid Ltd, Basingstoke, UK) and IL-2, then screened for peptide specificity in proliferation assays.22,31 The resulting T-cell clones were characterized with respect to peptide responses and HLA restriction in 3 H-thymidine incorporation assays.31 Briefly, the addition of blocking antibodies B7/21 (anti-HLA-DP), SPV-L3 (anti-HLA-DQ), and B8.11 (anti-HLA-DR) was used to determine the HLA-restriction of the T cell clones.31 Autologous EBV-LCLs were used as the antigen presenting cell line.
Polymorphism rs368234815 of interferon-λ4 gene and generation of antibodies to hepatitis B virus surface antigen in extracorporeal dialysis patients
Published in Expert Review of Vaccines, 2020
Alicja E. Grzegorzewska, Monika K. Świderska, Wojciech Marcinkowski, Adrianna Mostowska, Paweł P. Jagodziński
The same human leukocyte antigen DP gene (HLA-DP) polymorphisms contribute to HBV persistence after infection and non-response to HBV vaccine [17]. Undetectable or very low anti-HBs titers characterizes both these conditions [1]. The mentioned finding [17] suggests that the same HLA-DP polymorphisms may correlate (also may not casually associate) with the anti-HBs generation, independently on the source of HBsAg for induction of immunization (vaccination or infection). The 15-year cumulative probability of HBsAg loss was significantly lower in the IFNL4 rs368234815 ΔG allele possessors (producing IFNλ4) than in the carriers of the rs368234815 TT/TT genotype [8]. In our study, the ∆G/∆G genotype indicated a higher probability of non-responsiveness to HBV vaccination than the TT/TT genotype. Again, both these conditions (persistent HBsAg and non-responsiveness to HBV vaccination) are accompanied by undetectable or very low anti-HBs titers [1]. We compared the frequency of IFNL4 rs368234815 genotypes between all anti-HBs positive subjects (generated anti-HBs after vaccination or infection) and all anti-HBs negative patients (did not develop anti-HBs despite vaccination or infection). Although this procedure increased the number of subjects in each tested group, we did not obtain the statistical significance in the univariate analysis.