T cell immunophenotyping and rubella infection in HLA-I deficiency. (A) CD3⁺ T cell counts. (B) CD3⁺TCRγδ⁺ T cell counts. (C) CD3⁺TCRγδ⁻CD4⁺CD8⁻ and CD3⁺TCRγδ⁻CD4⁻CD8⁺ T cell counts. (D) Counts of naïve (CD45RA⁺CCR7⁺), central memory (CD45RA⁻CCR7⁺), effector memory (CD45RA⁻CCR7⁻), and TEMRA (CD45RA⁺CCR7⁻) CD4 T cells. (E) Counts of naïve (CD45RA⁺CCR7⁺), central memory (CD45RA⁻CCR7⁺), effector memory (CD45RA⁻CCR7⁻), and TEMRA (CD45RA⁺CCR7⁻) CD8 T cells. (F) Ratio CD4/CD8 in naïve (left) and memory (right) CD3⁺TCRγδ⁻ T cells. (G) MAIT (CD3⁺CD161⁺TCRva7.2⁺) and invariant NKT (CD3⁺iNKT⁺) unconventional ⍺β T cell counts. (H and I) Representation of anti-rubella IgG titers in IU/ml and (I) logarithmic scale with representation of the mean and standard deviation according to the decade of birth of the subjects. The orange dots represent the four patients of the present study (P1–P4 by chronological order of birth). The green dot corresponds to a recently reported patient with rubella granuloma and ITK deficiency (7). The blue dots correspond to the serological titers of all patients who had a rubella serology prescription at the Assistance Publique Hôpitaux de Marseille (excluding the obstetrics department) from 01/01/2022 to 31/12/2022 with negative IgM and detectable IgG (>20 IU/ml). (J) Phylogenetic analysis of rubella partial genome sequence of strain from patient 1 (PV855062). A total of 2,696 nucleotide sequences (positions 230–472, 636–861, 1087–1316, 3874–4125, 4522–4987, 5106–5344, 5528–5744, 6916–7160, 8328–8572, and 8741–9073 on reference NC_001545). (K) Phylogenetic analysis of rubella partial genome sequence of strain from patient 2 (PV855063). A total of 519 nucleotide sequences (positions 8569–9088 on reference NC_001545). (L) Phylogenetic analysis of rubella partial genome sequence of strain from patient 4 (PV855064). A total of 3,566 nucleotide sequences (positions 239–473, 1506–1680, 1794–2044, 3271–3668, 3936–4172, 4376–4606, 4802–5277, 5660–5900, 6915–7142, 7835–7887, and 8530–9570 on reference NC_001545). For all patients, nucleotide sequences were obtained directly from skin biopsies. Phylogenetic trees were constructed using MEGA7 software with the maximum likelihood method and the Tamura–Nei model. Bootstrap values (calculated with 1,000 replicates) lower than 75% are not shown, and those above 75% are indicated by an asterisk. RuV sequences belonging to clade 1 are shown in blue. The sequences in bold and darker blue correspond to RuVs responsible for chronic infections derived from the Wistar RA27/3 vaccine strain. Sequences in green belong to clade 2. The two sequences in bold and dark green correspond to two cases of chronic infection from wild-type strains. The patient’s sequences are in dark red.