HLA-G polymorphisms and molecule function - Questions and more questions -A review

Human leukocyte antigen (HLA)-G is a non-classical HLA-class I antigen whic h is predominantly expressed on invasive trophoblastic cells and is postula ted to be a mediator of maternal-fetal tolerance. HLA-G interacts with NK c ells, can present nonamer peptides and binds CD8 in an analogous manner to classical HLA-I. The HLA-G protein exists in soluble and membrane-bound iso forms generated through alternative splicing. Although initially considered to be non-polymorphic, variations of the HLA-G DNA sequence have been repo rted which led to the definition of a limited number of HLA-G alleles inclu ding the Null-allele G*0105N. Whereas the HLA-G DNA sequence shows a high degree of conservation in posit ions which are essential for classical HLA-I molecule functions, polymorphi c sites in HLA-G are not congruent with sites of high nucleotide variabilit y in classical HLA. The identification of two females with recurrent sponta neous abortions who are homozygous for the G*0105N Null-allele re-opens the discussion about the role of HLA-G in pregnancy and underlines the need of a systematic analysis of the different hypotheses of HLA-G function in viv o. (C) 2000 IFPA and Harcourt Publishers Ltd.