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Unusual expression of human lymphocyte antigen class II in normal renal microvascular endothelium
K A Muczynski1, T Cotner, S K Anderson
1Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington 98195, USA. kzynski@u.washington.edu
Background:
The human lymphocyte antigen (HLA) class II proteins (DR, DQ, and DP) and DM, a protein involved in loading antigenic peptide onto the class II molecules, have a coordinate regulation that facilitates antigen presentation to CD4+ T cells. CIITA is a specific transcription factor responsible for the coordinate regulation of these genes. DR expression in the kidney was described to be constitutive on renal microvascular endothelium in the early 1980s, but expression of other genes involved in class II antigen presentation (DQ, DP, DM, and CIITA) has not been characterized.
Methods:
Expression of the HLA class II proteins, DM, and CIITA in normal human kidney cortex was evaluated by immunofluorescence microscopy, Northern blots, and reverse transcriptase-polymerase chain reaction (RT-PCR).
Results:
The endothelium of glomerular and peritubular capillaries constitutively express DR, as indicated by colocalization of DR and CD31 antibodies. However, the endothelium of larger renal blood vessels is devoid of class II proteins. Capillaries that express DR do not have detectable DQ, DP, or DM by immunofluorescence. Northern blots identified DR, DP, and DM mRNAs but not DQ mRNA. CIITA was amplified by RT-PCR at a level that could account for the class II expressed by the microvascular endothelium.
Conclusion:
The renal microvascular endothelium constitutively expresses DR without the other class II proteins or DM. This discoordinate expression of HLA class II genes is unusual and may contribute to the kidney's ability to control CD4+ T-cell responses.