Thus, due to disrupted CD4/HLA class II interactions in the thymus, individuals with HLA class II deficiency have profound CD4+ T cell deficiency (10–20-fold reduction) and are consequently susceptible to a broad range of pathogens (Al-Herz et al., 2013; Ben-Mustapha et al., 2013; Ouederni et al., 2011; Rozmus et al., 2013). Here, CD4 is linked to congenital T-cell immunodeficiency.