Characterization of an HLA-DR15 DQ5 Haplotype Found in the Spanish Caucasoid Population Carlos Vilches, Rosario de Pablo, Maria E. Moreno, Rosario Solis, and Miguel Kreisler ABSTRACT: HLA class II typing by RFLP and PCR-SSOP has been performed on HLA-DR2-positive individuals as a part of a study on MHC in a Spanish Caucasoid population. The results of this study reveal that HLA-DR15 (DRBl*1501 DRB5*0101) and DQ5 (DQAI*0102 DQB1*0501/0502) are not uncommonly associated in such a population. Family segregation has been assessed and allogeneic reactivity against some classic DR2 haplotypes has been tested; a stimulatory capability of DQ6 antigen in this situation is shown. It is suggested that the reported association is not uncommon in Euro- pean Caucasoids as well as in other populations and it should be considered in matching for transplantation and in DR2-associated diseases. Human Immunology 35, 223-229 (1992) ABBREVIATIONS MHC major histocompatibility complex MLC mixed lymphocyte culture Na2EDTA ethylenediamine tetraacetic acid, disodium salt PCR polymerase chain reaction RFLP SDS SSOP TMAC restriction fragment length polymorphism sodium dodecyl sulfate sequence-specific oligonucleotide probe tetramethylammonium chloride INTRODUCTION HLA-DR2 is one of the most common antigens in Cauca- soid populations. Increased as well as decreased frequen- cies of DR2 have been found in diseases such as multiple sclerosis [1], narcolepsy [2], and insulin-dependent dia- betes mellitus [3], and in immunologic states of respon- siveness to certain antigens [4]. DR2 splits into two variants, namely DR15 (DR2 long) and DR16 (DR2 short). The former is considered to be strongly associated to HLA-DQ6(1) in Caucasoids and corresponds to the cellular defined specificities Dw2 and Dw12, depending on the DRB, DQB, and DQA alleles expressed [5]. DR16 is more frequently linked to DQ5(1)--correlating with Dw21--and rarely to DQ7(3)--Dw22. These associations and variants can be From the Department of Immunology, Puerta de Hierro Hospital, Ma- drid, Spain. Address reprint requests to Dr. C. Vilches, Servicio de Inmunologla, Hospital Puerta de Hierro, San Martin de Porres 4, 28035 Madrid, Spain. Received March 26," accepted August 1 O, 1992. easily recognized by means of restriction fragment length polymorphism (RFLP) [6-8] and polymerase chain reaction and sequence-specific oligonucleotide probe (PCR-SSOP) [9], techniques that, in addition, have allowed the description of new variants for DR2, mainly in non-Caucasoid populations [10, 11], and dif- ferent exceptions to the aforementioned associations. For instance, DR15 antigen, including the newly de- scribed DRBl*1503 allelle [12], has been reported to be associated with DQ5 in different populations [9, 13-17 ]. Nevertheless, DR 15 DQ 5 has not been consid- ered a typical linkage among Occidental Caucasoids to date. To further characterize major histocompatibility com- plex (MHC) class II antigens and haplotypes in the Span- ish population and to describe their frequencies as healthy controls for possible HLA-disease associations, we have performed serologic, RFLP, and PCR-SSOP typing on 127 unrelated healthy individuals. An unex- pected occurrence of DR15 associated with DQ5 has been found. Human Immunology 35, 223-229 (1992) 223 © American Society for Histocompatibility and Immunogenetics, 1992 0198-8859/92/$5.00