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Major histocompatibility complex (MHC) genes (referred to as human leukocyte antigen or HLA in humans) are a key component of vertebrate immune systems, coding for proteins which present antigens to T‐cells. These genes are outstanding in their degree of polymorphism, with important consequences for human and animal health. The polymorphism is thought to arise from selection pressures imposed by pathogens on MHC allomorphs, which differ in their antigen‐binding capacity. However, the existing theory has not considered MHC selection in relation to the formation of immune memory. In this paper, we argue that this omission limits our understanding of the evolution of MHC polymorphism and its role in disease. We review recent evidence that has emerged from the massive research effort related to the SARS‐CoV‐2 pandemics, and which provides new evidence for the role of MHC in shaping immune memory. We then discuss why the inclusion of immune memory within the existing theory may have non‐trivial consequence for our understanding of the evolution of MHC polymorphism. Finally, we will argue that neglecting immune memory hinders our interpretation of empirical findings, and postulate that future studies focusing on pathogen‐driven MHC selection would benefit from stratifying the available data according to the history of infection (and vaccination, if relevant). [ABSTRACT FROM AUTHOR]

Many specificities single out HLA‐F: its structure, expression regulation at cell membrane and function. HLA‐F mRNA is detected in the most cell types and the protein is localized in the ER and Golgi apparatus. When expressed at cell surface, HLA‐F may be associated to β2‐microglobulin and peptide or expressed as an open‐conformer molecule. HLA‐F reaches the membrane upon activation of different primary cell types and cell‐lines. HLA‐F has its highest affinity for the KIR3DS1‐activating NK receptor, but also binds inhibitory immune receptors. Some studies reported that HLA‐F expression is associated with its genotype. Higher HLA‐F mRNA expression associated with F*01:01:02, and 3 noncoding SNPs, rs1362126, rs2523405, and rs2523393, located in HLA‐F‐AS1 or upstream the HLA‐F sequence were associated with HLA‐F mRNA expression. Given the implication of HLA‐F in many clinical setting, and the undisclosed process of its expression regulation, we aim to confirm the effect of the aforementioned SNPs with HLA‐F transcriptional and protein expression. We analyzed the distribution, frequency and linkage disequilibrium of these SNPs at worldwide scale in the 1000 Genomes Project samples. Influence on the genotype of each SNP on HLA‐F expression was explored using RNAseq data from the 1000 Genomes Project, and using Q‐PCR and intracellular cytometry in PBMC from healthy individuals. Our results show that the SNPs under studied displayed remarkably different allelic proportion according to geography and confirm that rs1362126, rs2523405, and rs2523393 displayed the most concordant results, with the highest effect size and a double‐dose effect. [ABSTRACT FROM AUTHOR]

We describe the novel KIR3DL1*182 allele and confirmed the 3DL1*15002 allele. [ABSTRACT FROM AUTHOR]

Uncontrolled inflammation of the airways in chronic obstructive lung diseases leads to exacerbation, accelerated lung dysfunction and respiratory insufficiency. Among these diseases, asthma affects 358 million people worldwide. Human bronchial epithelium cells (HBEC) express both anti‐inflammatory and activating molecules, and their deregulated expression contribute to immune cell recruitment and activation, especially platelets (PLT) particularly involved in lung tissue inflammation in asthma context. Previous results supported that HLA‐G dysregulation in lung tissue is associated with immune cell activation. We investigated here HLA‐F expression, reported to be mobilised on immune cell surface upon activation and displaying its highest affinity for the KIR3DS1‐activating NK receptor. We explored HLA‐F transcriptional expression in HBEC; HLA‐F total expression in PBMC and HBEC collected from healthy individuals at rest and upon chemical activation and HLA‐F membrane expression in PBMC, HBEC and PLT collected from healthy individuals at rest and upon chemical activation. We compared HLA‐F transcriptional expression in HBEC from healthy individuals and asthmatic patients and its surface expression in HBEC and PLT from healthy individuals and asthmatic patients. Our results support that HLA‐F is expressed by HBEC and PLT under healthy physiological conditions and is retained in cytoplasm, barely expressed on the surface, as previously reported in immune cells. In both cell types, HLA‐F reaches the surface in the inflammatory asthma context whereas no effect is observed at the transcriptional level. Our study suggests that HLA‐F surface expression is a ubiquitous post‐transcriptional process in activated cells. It may be of therapeutic interest in controlling lung inflammation. [ABSTRACT FROM AUTHOR]

We describe nine novel HLA‐J alleles validated by in silico and experimental data. [ABSTRACT FROM AUTHOR]

We isolated 11 novel HLA alleles in the 1000 Genomes Project using PolyPheMe software. [ABSTRACT FROM AUTHOR]

We describe the full gene sequences of 15 HLA‐H alleles. [ABSTRACT FROM AUTHOR]

We describe nine novel HLA‐F alleles. [ABSTRACT FROM AUTHOR]