В основе реакции иммунологического отторжения аллогенного трансплантата лежит процесс распознавания донорских антигенов Т-клеточными рецепторами. В качестве антигенов, как правило, выступают молекулы главного комплекса гистосовместимости, экспрессированные клетками тканей донорского органа. По своей активности иммунный ответ на аллогенный трансплантат в значительной степени превышает реакцию на обычную инфекцию и характеризуется стойкой иммунологической памятью. При этом базовые механизмы распознавания антигена при инфекции и аллотрансплантации, по-видимому, должны быть сходными. В данном обзоре рассматриваются три основных пути распознавания аллоантигенов, принципиально различающиеся природой антигенпрезентирующих клеток, кинетикой и продолжительностью своего влияния на формирование аллоиммунитета: прямой, непрямой и смешанный. Установление взаимосвязи механизмов аллораспознавания с проявлениями реакции отторжения трансплантата имеет важное клиническое значение.
The main histocompatibility complex — HLA system (Human Leukocyte Antigens) is among the most important genetic factors determining response of humans to infectious agents. The key role that HLA molecules play in immune response is to present the pathogen-derived peptides. Enormous molecular variability of HLA alleles in human populations have attracted close attention and became the basis for numerous studies aimed at evaluating the role of HLA genotypes for individual features of immune response to COVID-19, the new infection caused by SARS-CoV-2 β-coronavirus. Many studies have focused on search of specific alleles associated with both susceptibility and resistance to this disease. Separate HLA patterns were reported already. These patterns may be either universal to several populations, or rather peculiar, since distribution of HLA genes is different for various populations, depending on the living conditions, including specific protection from environmental pathogens. Therefore, it is evident that individual effects of HLA genotype upon occurrence and course of SARS-CoV-2 infection should be performed in comparison with the HLA distribution among the residents of appropriate region. The objective of this study was to compare the distribution of HLA-A*, B*, DRB1* allele groups, and to analyze the frequencies of HLA-AB-DRB1 haplotypes in subjects with COVID-19 (n = 138), compared with the control group presented by residents of the North-Western Russia (n = 1456). The most significant differences between COVID-19 patients compared with a group from control population were revealed for the groups of HLA-A* alleles: the frequencies of HLA-A*02 and HLA-A*26 were significantly reduced (39.86% versus 51.72%, χ2 = 7,58, and 4.35% versus 9.07%, χ2 = 4.17, respectively). At the same time, the frequency of HLA-A*29 was increased more than 2-fold (5.80% versus 2.47%, χ2 = 4.03). This finding suggests that the allele groups A*02 and A*26 are associated with reduced likelihood of the disease, while A*29, is an apparent factor predisposing for susceptibility to the disease. It was found that occurrence of definite HLA haplotypes, including the A*02 allele group, is less common in persons who have undergone COVID-19, and are ranged at the 4th, 7th and 10th positions in frequency, while in the population control group such HLA haplotypes took the 3rd, 4th, 7th and 8th places. Further evaluation of the HLA gene polymorphism will allow to understand the predetermined immunogenetic basis for susceptibility, as well as clinical severity of COVID-19.
As a result of the study, statistically significant differences in the distribution of HLA-DRB1* alleles in children with TB in comparison with a control group for *01, *03, *11, *13, *07, *15, and *16 alleles were found. It may indicate their protective role in the development of TB. DRB1 *07 and *15 alleles were observed significantly rare in children with single TB than in children with generalized TB and healthy controls.
1 ФГБУ «Российский НИИ гематологии и трансфузиологии ФМБА России», Санкт-Петербург, Российская Федерация 2 ФГБУ «Северо-Западный федеральный медицинский исследовательский центр» Минздрава России, Санкт-Петербург, Российская Федерация Проблема гуморального, антителоопосредованного отторжения донорского органа остается крайне ак-туальной. Главной мишенью антител в основном являются донорские HLA-антигены (Human Leucocyte Antigens), экспрессируемые, в частности, клетками сосудистого эндотелия трансплантата. В данном обзоре рассматриваются механизмы развития гуморального аллоиммунитета, в основе которых лежит распознавание В-клетками реципиента эпитопов донорских HLA-молекул и созревание аффинности В-клеточных рецепторов в герминативных центрах периферической лимфатической системы. Учет по-казателей эпитопной нагрузки и кросс-реактивности при анализе HLA-совместимости донора и реципи-ента играет важную роль в профилактике гуморального отторжения аллогенного трансплантата.Ключевые слова: гуморальное отторжение, аллогенный трансплантат, HLAантигены, Вклеточные рецепторы, герминативные центры, эпитопы, кроссреактивность.
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