DOI: 10.5061/dryad.p8cz8w9vw
title: Data for: The CD4 transmembrane GGXXG and juxtamembrane (C/F)CV+C motifs mediate pMHCII-specific signaling independently of CD4-Lck interactions

description: We previously reported that the transmembrane GGXXG motif co-arose with
 the cytoplasmic juxtamembrane (C/F)CV+C motif in eutherian (placental
 mammal) CD4 and that constituent residues therein evolve under purifying
 selection (Lee, et al., 2022). These data led us to discover that mutating
 these motifs together increased CD4-Lck association but reduced CD3z,
 Zap70, and Plcg1 phosphorylation levels as well as IL-2 production.
 Because these mutants preferentially localized CD4-Lck pairs to
 non-membrane raft fractions, one potential explanation for our results was
 that they impaired proximal signaling by sequestering Lck away from
 TCR-CD3. An alternative hypothesis is that the mutations directly impacted
 TCR-CD3 signaling because the wild type motifs play a Lck-independent role
 in signaling. Here we used a reductionist approach to discriminate between
 these possibilities (Lee, et al., 2023). Our current data lead us to
 conclude that: intracellular CD4-Lck interactions are not necessary for
 pMHCII-specific signal initiation; the GGXXG and (C/F)CV+C motifs are key
 determinants of CD4-mediated pMHCII-specific signal amplification; the
 GGXXG and (C/F)CV+C motifs exert their functions independently of direct
 CD4-Lck association. These data provide a mechanistic explanation for why
 residues within these motifs are under purifying selection. The results
 are also important to consider for biomimetic engineering of synthetic
 receptors.
description: Methods are described in the manuscript
description: excel or any text editor
description: # Data for The CD4 transmembrane GGXXG and juxtamembrane (C/F)CV+C motifs
 mediate pMHCII-specific signaling independently of CD4-Lck interactions
 Data associated with the statistical analyses described. Each figure has a
 separate file. Data was exported from Prism ## Description of the data and
 file structure Data associated with the statistical analyses described in
 the paper. Each figure has a separate file. specific figure is indicated
 in the title of the file Data was exported from Prism and is provides as
 an excel file. Figure_2_stats_export.xlsx: contains the raw values used
 for the experiment described in Figure 2 SFig_3_stat_export.xlsx: contains
 the raw values used for the experiment described in Supplementary Figure 3
 Figure_3_stats_export.xlsx: contains the raw values used for the
 experiment described in Figure 3 Figure_4_stats_export.xlsx: contains the
 raw values used for the experiment described in Figure 4
 Figure_5_stats_export.xlsx: contains the raw values used for the
 experiment described in Figure 5 SFig_2_Stats_export.xlsx: contains the
 raw values used for the experiment described in Supplementary Figure 2
 SFig_5_stats_export.xlsx: contains the raw values used for the experiment
 described in Supplementary Figure 5 SFig_4_stat_export.xlsx: contains the
 raw values used for the experiment described in Supplementary Figure 4
 master_intensity_and___responders_work_sheet_for_normalization.xlsx:
 Describes the logic used to normalize the data