Human body●●●●●Difficulty 3 of 5

How does your body spot a cell that a virus has secretly taken over?

Two scientists found the answer by infecting mice with a meningitis virus, and won a Nobel Prize for discovering your cells wear an ID tag.

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Nearly every cell in your body constantly displays tiny fragments of its own proteins on its surface, like a running photo ID, using molecules called MHC class I. If a virus infects the cell and forces it to make viral proteins, fragments of those viral proteins get displayed too. A killer T cell patrolling nearby checks that display. If it recognizes a viral fragment riding on an MHC molecule, it destroys the infected cell on the spot.

How a killer T cell spots an infected cell
  1. Step 1: Virus hides inside

    It forces the cell to make viral proteins

  2. Step 2: MHC displays fragments

    Pieces of those proteins reach the cell surface

  3. Step 3: T cell checks the ID

    Its receptor scans for a matching viral fragment

  4. Step 4: Double match required

    Viral fragment + self MHC, together, on the same cell

  5. Step 5: Cell destroyed

    The killer T cell eliminates the infected cell

Scientists already knew MHC molecules existed, because they are what makes organ transplants succeed or fail: the immune system rejects tissue from a badly mismatched donor. But working with mice infected by a meningitis virus in the 1970s, Peter Doherty and Rolf Zinkernagel found something stranger. A killer T cell only recognized an infected cell when it detected the viral fragment and a matching self MHC molecule at the same time, never either alone. The discovery won them the 1996 Nobel Prize in Physiology or Medicine.

The same ID system is why transplants need compatible donors. The human version of MHC, called HLA, comes in more than 17,000 known variants, so it is extremely uncommon for any two unrelated people to carry identical copies.

Quiz me

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  1. 1.What two things does a killer T cell need to detect at once to destroy an infected cell?
  2. 2.What were MHC molecules first known for, before Doherty and Zinkernagel's discovery?
  3. 3.Why is finding a well-matched organ donor so difficult?

Recap

A killer T cell destroys a cell only when it recognizes both a foreign fragment and a matching self MHC molecule displayed together on that cell's surface.

Surprising fact · Doherty and Zinkernagel showed a killer T cell needs to detect a viral fragment and a matching self MHC molecule on the same cell at once, work that won the 1996 Nobel Prize.

Sources (5)

No source, no claim. Every fact in this lesson (13 claims) cites at least one of these.

  1. [1]Major histocompatibility complex · Wikipedia
  2. [2]Cytotoxic T cell · Wikipedia
  3. [3]Peter C. Doherty · Wikipedia
  4. [4]Rolf M. Zinkernagel · Wikipedia
  5. [5]Transplant rejection · Wikipedia
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