RT Journal Article
T1 Evolution and molecular interactions of major histocompatibility complex (MHC)-G, -E and -F genes
A1 Suarez-Trujillo, Fabio
A1 Juarez, Ignacio
A1 Rodríguez-Sainz, Carmen
A1 Vaquero Yuste, Christian
A1 Palacio-Gruber, José
A1 Molina-Alejandre, Marta
A1 Fernández-Cruz, Eduardo
A1 Martín Villa, José Manuel
A1 Arnaiz Villena, Antonio
A1 Juárez Martín-Delgado, Ignacio
A1 Fernández-Cruz Pérez, Eduardo
AB <jats:title>Abstract</jats:title><jats:p>Classical<jats:italic>HLA</jats:italic>(Human Leukocyte Antigen) is the Major Histocompatibility Complex (MHC) in man. HLA genes and disease association has been studied at least since 1967 and no firm pathogenic mechanisms have been established yet.<jats:italic>HLA-G</jats:italic>immune modulation gene (and also<jats:italic>-E</jats:italic>and<jats:italic>-F</jats:italic>) are starting the same arduous way: statistics and allele association are the trending subjects with the same few results obtained by<jats:italic>HLA</jats:italic>classical genes, i.e., no pathogenesis may be discovered after many years of a great amount of researchers’ effort. Thus, we believe that it is necessary to follow different research methodologies: (1) to approach this problem, based on how evolution has worked maintaining together a cluster of immune-related genes (the MHC) in a relatively short chromosome area since amniotes to human at least, i.e., immune regulatory genes (MHC-G, -E and -F), adaptive immune classical class I and II genes, non-adaptive immune genes like (C2, C4 and Bf) (2); in addition to using new in vitro models which explain pathogenetics of<jats:italic>HLA</jats:italic>and disease associations. In fact, this evolution may be quite reliably studied during about 40 million years by analyzing the evolution of<jats:italic>MHC-G, -E, -F</jats:italic>, and their receptors (KIR—killer-cell immunoglobulin-like receptor, NKG2—natural killer group 2-, or TCR-T-cell receptor—among others) in the primate evolutionary lineage, where orthology of these molecules is apparently established, although cladistic studies show that<jats:italic>MHC-G</jats:italic>and<jats:italic>MHC-B</jats:italic>genes are the ancestral class I genes, and that New World apes<jats:italic>MHC-G</jats:italic>is paralogous and not orthologous to all other apes and man<jats:italic>MHC-G</jats:italic>genes. In the present review, we outline past and possible future research topics: co-evolution of adaptive<jats:italic>MHC</jats:italic>classical (class I and II), non-adaptive (i.e., complement) and modulation (i.e., non-classical class I) immune genes may imply that the study of full or part of MHC haplotypes involving several loci/alleles instead of single alleles is important for uncovering HLA and disease pathogenesis. It would mainly apply to starting research on HLA-G extended haplotypes and disease association and not only using single HLA-G genetic markers.</jats:p>
PB Springer Link
SN 1420-682X
SN 1420-9071
YR 2022
FD 2022-08
LK https://hdl.handle.net/20.500.14352/92346
UL https://hdl.handle.net/20.500.14352/92346
LA eng
DS Docta Complutense
RD 5 abr 2025