Publication: KIR2DL5: contribución a la diversidad del complejo de genes "KIR", expresión diferencial de sus alelos y distribución de potenciales ligandos
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2017-09-04
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Universidad Complutense de Madrid
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Abstract
El polimorfismo alélico y la variación en el número de copias confieren una elevada diversidad a los genotipos KIR. El complejo KIR incluye sólo tres bloques relativamente bien conservados: los genes en los extremos centromérico (KIR3DL3) y telomérico (KIR3DL2) y la agrupación central (KIR3DP1-2DL4). Dichos bloques flanquean dos regiones que contienen distintas combinaciones del resto de genes KIR. Además, combinaciones de genes KIR atípicas que presentan deleciones, inserciones y genes de fusión contribuyen a la variabilidad del complejo. La distribución de las combinaciones de genes KIR que se heredan juntas en un orden dado (“haplotipos KIR”) varía notablemente entre distintas poblaciones. Un ejemplo de polimorfismo alélico y variación en el número de copias es KIR2DL5, el KIR más recientemente descrito en humanos, que se expresa en subpoblaciones de linfocitos T y células NK. Junto con KIR2DL4 son los dos únicos miembros de un linaje ancestral de KIR con dominios tipo Ig D0-D2, lo que los distingue del resto de KIR2Ds, con dominios D1-D2 que reconocen moléculas HLA-C. KIR2DL5 está representado en el genoma por dos genes, el telomérico KIR2DL5A y el centromérico KIR2DL5B, ambos presentan variación en el número de copias. Mientras que el ARNm de la mayoría de alelos KIR2DL5B es indetectable, KIR2DL5A es transcrito normalmente. Sin embargo, la expresión en superficie de KIR2DL5, determinada mediante citometría de flujo con el AcMo UP-R1, no es detectada en todos los individuos que presentan un gen KIR2DL5A transcrito, lo que está relacionado con el polimorfismo alélico...
Allelic polymorphism and copy-number variation confer enormous diversity to human KIR genotypes. The KIR complex includes only three relatively well-conserved blocks: the genes at its centromeric (KIR3DL3) and telomeric (KIR3DL2) ends and the central cluster (KIR3DP1-2DL4). These flank two regions containing variable combinations of all other KIR genes. Furthermore, unusual KIR-gene combinations that present deletions, insertions and fusion genes (many of them coding for new proteins with new features and functions) contribute to the variability of the KIR complex. The distribution of KIR-gene combinations (“KIR haplotypes”) varies remarkably in different ethnic groups and world regions. An example of copy number variation and allelic polymorphism is KIR2DL5; the most recently described human KIR. It is expressed on generally small subsets of NK and T lymphocytes. KIR2DL4 and KIR2DL5 are the only members of an ancestral linage of KIR with immunoglobulin-like domains of the D0-D2 type, which distinguishes them from all other KIR2Ds, having domains of the D1-D2 type that recognize HLA-C molecules. KIR2DL5 is represented in the human Leukocyte Receptor Cluster by two genes, the telomeric KIR2DL5A and the centromeric KIR2DL5B, both of which show copy-number variation...
Allelic polymorphism and copy-number variation confer enormous diversity to human KIR genotypes. The KIR complex includes only three relatively well-conserved blocks: the genes at its centromeric (KIR3DL3) and telomeric (KIR3DL2) ends and the central cluster (KIR3DP1-2DL4). These flank two regions containing variable combinations of all other KIR genes. Furthermore, unusual KIR-gene combinations that present deletions, insertions and fusion genes (many of them coding for new proteins with new features and functions) contribute to the variability of the KIR complex. The distribution of KIR-gene combinations (“KIR haplotypes”) varies remarkably in different ethnic groups and world regions. An example of copy number variation and allelic polymorphism is KIR2DL5; the most recently described human KIR. It is expressed on generally small subsets of NK and T lymphocytes. KIR2DL4 and KIR2DL5 are the only members of an ancestral linage of KIR with immunoglobulin-like domains of the D0-D2 type, which distinguishes them from all other KIR2Ds, having domains of the D1-D2 type that recognize HLA-C molecules. KIR2DL5 is represented in the human Leukocyte Receptor Cluster by two genes, the telomeric KIR2DL5A and the centromeric KIR2DL5B, both of which show copy-number variation...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 07-11-2016