T cell immunodominance is dictated by the positively selecting self-peptide
- Washington University School of Medicine, United States
Figures
Figure 1
The I-Ekα and covalently-linked gp250/I-Ekβ transgenes restore surface expression of I-Ek in gp250 SC mice class II-deficient mice.
The surface expression of I-Ek on B cells (A and B) and dendritic cells (C and D) from the spleens of gp250 SC mice. The B cells and dendritic cells from MHCII−/−CD74−/− mice were used as negative …
Figure 2 with 1 supplement
The single gp250/I-Ek ligand positively selects a significant population of CD4+ T cells in gp250 SC mice.
(A) Total number of thymocytes in B6.K or gp250 SC mice. (B) Plot of thymocytes from B6.K or gp250 SC mice. (C and D) Quantification by percentage of CD4SP (C) or CD8SP (D) thymocytes, and of total …
Figure 2—figure supplement 1
TCR Vβ usages of peripheral T cells in gp250 SC mice.
(A and B) Vβs expression of peripheral CD4+ T cells in B6.K or gp250 SC mice. The frequencies of three Vβs were decreased (A) and three were increased (B). n = 9; data are representative of three …
Figure 3
gp250-mediated positive selection greatly expands MCC-tetramer+ CD4+ T cells.
(A and B) The frequency of MCC-tetramer+ CD4SP thymocytes or peripheral CD4+ T cells in B6.K or gp250 SC mice. The plot was gated on the live CD4+CD3+CD8− population. The data are representative of …
Figure 4
The majority of gp250-selected MCC-specific CD4+ T cells express Vα11+ TCR.
(A and B) The Vα11 expression of MCC-tetramer+ peripheral CD4+ T cells in B6.K or gp250 SC mice. (B) n = 6; mean ± SD; two-tailed Mann–Whitney test. (C and D) The CD69 upregulation of sorted …
Figure 5
The gp250 self-peptide skews the selection of MCC-reactive preferred TCR pairs.
(A) The Vα11 and Vβ3 expression of thymic CD4SP or peripheral CD4+ T cells in B6.K or gp250 SC mice. The data are representative of three experiments. (B) The quantification by percentage of Vα11+ …
Figure 6
The gp250 self-peptide skews the selection of TCRs exhibiting conserved MCC-reactive features.
(A) The pie chart of amino acid usages at CDR3 α89 and α91 of bulk-sorted peripheral Vα11+Vβ3+ CD4+ T cells in B6.K or gp250 SC mice. The gp250 SC data were obtained by single cell repertoire …
Figure 7
The evolving concepts of the relationship between positively selecting self-peptide and post-selection T cell repertoire.
The figures show the progress of our understanding about the relationship between thymic self-peptides and post-selection CD4+ T cell repertoire, and are arranged in chorological order. The first …
Tables
Table 1
Examples of CDR3α sequences of Vα11+Vβ3+ CD4+ T cells from gp250 SC mice in the single cell repertoire analysis
| CDR3α sequences | Jα usages | Frequency | Notes |
|---|---|---|---|
| CAAEASSGSWQLIF | TCRA17 | 21% (8/38) | Also published in McHeyzer-Williams et al. (1999) |
| CAAEANSGTYQRF | TCRA11 | 7.8% (3/38) | |
| CAAEAGGGSGGKLTL | TCRA36 | 5.2% (2/38) | |
| CAAEASSGQKLVF | TCRA13 | 5.2% (2/38) | AND TCR CDR3α; also published in McHeyzer-Williams et al. (1999) |
| CAAEPPHANTGANTGKLTF | TCRA44 | 5.2% (2/38) | |
| CAANTGNYKYVF | TCRA33 | 5.2% (2/38) | |
| CAADRSNNRIFF | TCRA24 | 5.2% (2/38) | |
| CAAEPSSFSKLVF | TCRA24 | 2.6% (1/38) | |
| CAAESSNMGYKLTF | TCRA8 | 2.6% (1/38) | |
| CAARSSNTNKVVF | TCRA8 | 2.6% (1/38) |
Table 2
The single cell repertoire analysis of Vα11+Vβ3+ CD4+ T cells from gp250 SC mice
| CDR3α sequences | Jα usages | CDR3β sequences | Jβ usages |
|---|---|---|---|
| CAADRSNNRIFF | TCRA17 | CASSKQANSYNSPLYF | Jβ2.4 |
| CAAESSNMGYKLTF | TCRA24 | CASSGDGRGNTLYF | Jβ1.8 |
| CAARSSNTNKVVF | TCRA27 | CASSLWANTGQLYF | Jβ2.2 |
| CAAEANSGTYQRF | TCRA11 | CASSLLHKQYF | Jβ2.1 |
| CAAEASSGSWQLIF | TCRA17 | CASSPGTQNTLYF | Jβ2.4 |
Table 3
The CDR3 sequences of bulk-sorted Vα11+Vβ3+ CD4+ T cells from gp250 SC mice that overlap with the published data from normal mice (Hedrick et al., 1988; McHeyzer-Williams et al., 1999)
| Published CDR3α (Hedrick et al., 1988; McHeyzer-Williams et al., 1999) | Current study | Notes | |
|---|---|---|---|
| B6.K | SC | ||
| 3623 | 2906 | Unique sequences | |
| CAAEASSGQKLVFG | + | + | AND TCR |
| CAAEPSSGQKLVFG | + | + | 226 TCR |
| CAAEASGSWQLIFG | + | + | |
| CAAEASNTNKVVFG | + | + | 5c.c7 TCR |
| CAAEGSNTNKVVFG | + | ||
| CAAEASAGNKLTFG | + | + | |
| CAAASSGSWQLIFG | + | + | |
| CAAEAGSNAKLTFG | + | + | |
| CAAEASNNNAPRFG | + | ||
| CAAEAASLGKLQFG | + | + | |
| CAAEASSGSWQLIFG | + | + | |
| CAAEASNYNVLYFG | + | + | |
| CAAEASSSFSKLVFG | + | + | |
| CAAEASNMGYKLTFG | + | + | |
| CAAETGGYKVVFG | + | + | |
| CAAEANYNQGKLIFG | + | + | |
| CAAEAGSGTYQRFG | + | + | |
| CAGLSGSFNKLTFG | + | + | |
| CAAEGNTGNYKYVFG | + | ||
| CAAEEGNMGYKLTFG | + | + | |
| CAATSSGQKLVFG | + | ||
| Published CDR3β (Hedrick et al., 1988; McHeyzer-Williams et al., 1999) | Current study | Notes | |
|---|---|---|---|
| B6.K | SC | ||
| 2821 | 1583 | Unique sequences (mean) | |
| CASSLNSANSDY | + | AND, 5c.c7, 226 TCRs | |
| CASSLNNANSDY | + | + | |
| CASSLSTSQNTLYF | + | ||
| CASSLQGTNTEVFF | + | + | |
| CASRLGQNTLYF | + | ||
| CASSLGASAETLYF | + | ||
