Anti-HLA Alloantibody Is Found in Children But Does Not Correlate with a Lack of HIV Type 1 Transmission from Infected Mothers

Abstract

Searching for mechanisms of natural resistance to HIV infection with which to guide HIV vaccine design, we have examined antibody responses to HLA class I antigens in children of HIV-1-infected mothers. Anti-HLA antibodies are known to block HIV infectivity in vitro and can be protective against SIV challenge in macaques immunized with purified class I HLA. It was hypothesized that alloantibody to maternal HLA in children might contribute to the prevention of mother-to-child transmission of HIV-1. In fact, a surprisingly high proportion of the children examined, 22%, were found to have antibody against class I alloantigens. This alloantibody, however, did not correlate with the HIV status of the children and was found in a similar proportion of children of HIV-negative mothers. The HLA specificity of the antibody was not correlated with noninherited maternal HLA alleles and occurred with a higher frequency in older children. This result suggests environmental factors, rather than exposure to maternal cells, are involved in the formation of the alloantibody. The finding that anti-allo-class I HLA antibodies are not associated with a decreased risk of mother-to-child transmission indicates that this humoral immune response is unlikely to be the natural mechanism that accounts for the lack of transmission observed in many births. This result, however, does not preclude the further investigation of cellular alloimmune responses, or the use of alloimmunization as an artificial HIV immunization strategy.

Suppressed cellular alloimmune responses in HIV-exposed seronegative female sex workers

“…These findings confirm previous studies in Nairobi that did not find higher frequencies of class I antibodies among ESN FSWs or HIVnegative children born to seropositive mothers [13,14]. However, they are at variance with higher class I antibody levels detected among ESN drug users and in HIV-discordant couples [44,45].…”

“…However, the alloimmune responses that are expected to result from these particular HLA polymorphisms in ESN subjects have been more difficult to detect. Anti-HLA class I alloantibodies found in FSWs and in children born to HIV-infected mothers did not correlate with HIV protection [13,14]. To date, cellular alloimmune responses and their role in protection against HIV have not been studied in ESN subjects.…”

Therapeutic preparations of IVIg contain naturally occurring anti–HLA-E antibodies that react with HLA-Ia (HLA-A/-B/-Cw) alleles

“…Consequently, it may contain HLA antibodies because several allo-HLA antibodies are known to occur naturally in the sera of both men (nonalloimmunized) and women. [9][10][11][12][13] MoralesBuenrostro et al 11 demonstrated the specificities and incidence of these allo-HLA-I Abs in nonalloimmunized males. Neither the origin nor cause of anti-HLA Abs occurring in healthy individuals has been established.…”

Quantitation of HLA Proteins Incorporated by Human Immunodeficiency Virus Type 1 and Assessment of Neutralizing Activity of Anti-HLA Antibodies

“…In some studies, however, no protective role of anti-HLA antibodies against HIV-1 was observed. Anti-HLA alloantibodies found in children did not correlate with a lack of HIV-1 transmission from the infected mother (16). Similarly, the presence of anti-HLA antibodies did not correlate with resistance to HIV-1 infection by female commercial sex workers in the Nairobi cohort (17).…”